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Our scientific, training and research focus is to develop “state of the art” methods/procedures/tools/models for quantifying/studying the in vivo integrity and modulation of the blood brain barrier/neurovascular unit (BBB/NVU).<br /><div class="js-profile-less-about u-linkUnstyled u-tcGrayDarker u-textDecorationUnderline u-displayNone">less</div></div></div><div class="ri-section"><div class="ri-section-header"><span>Interests</span></div><div class="ri-tags-container"><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="38289730" href="https://www.academia.edu/Documents/in/Cardiac_Surgery"><div id="js-react-on-rails-context" style="display:none" 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data-dom-id="Pill-react-component-f5759ee8-7727-4e7c-b211-f799e2711746"></div> <div id="Pill-react-component-f5759ee8-7727-4e7c-b211-f799e2711746"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="38289730" href="https://www.academia.edu/Documents/in/Vitamin_D"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Vitamin D"]}" data-trace="false" data-dom-id="Pill-react-component-95d06c6b-6592-48fd-abb9-bb3a943297dd"></div> <div id="Pill-react-component-95d06c6b-6592-48fd-abb9-bb3a943297dd"></div> </a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Thomas Davis</h3></div><div class="js-work-strip profile--work_container" data-work-id="98172630"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172630/Effects_of_indomethacin_and_meclofenamate_on_renin_release_and_renal_hemodynamic_function_during_chronic_sodium_depletion_in_conscious_dogs"><img alt="Research paper thumbnail of Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs" class="work-thumbnail" src="https://attachments.academia-assets.com/99596403/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172630/Effects_of_indomethacin_and_meclofenamate_on_renin_release_and_renal_hemodynamic_function_during_chronic_sodium_depletion_in_conscious_dogs">Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs</a></div><div class="wp-workCard_item"><span>Circulation Research</span><span>, 1980</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We studied the control of renin release and renal hemodynamic function by administering prostagla...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. This high level of PRA after blockade of the adre...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="379ff8120487c9a2727cd7a1069e2471" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596403,"asset_id":98172630,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596403/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172630"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172630"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172630; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172630]").text(description); $(".js-view-count[data-work-id=98172630]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172630; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172630']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172630, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "379ff8120487c9a2727cd7a1069e2471" } } $('.js-work-strip[data-work-id=98172630]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172630,"title":"Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs","translated_title":"","metadata":{"abstract":"We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. 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profile--work_container" data-work-id="98172533"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172533/Inflammatory_pain_alters_blood_brain_barrier_permeability_and_tight_junctional_protein_expression"><img alt="Research paper thumbnail of Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression" class="work-thumbnail" src="https://attachments.academia-assets.com/99596348/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172533/Inflammatory_pain_alters_blood_brain_barrier_permeability_and_tight_junctional_protein_expression">Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2001</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, λ-carrageenan, or complete Freund&#39;s adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of sucrose into the cerebral hemispheres. Capillary depletion and cerebral blood flow analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Western blot analyses showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the λ-carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. Claudin-1 protein expression was present at...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f47aa4d94d79b02a60d547a121e4ab1c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596348,"asset_id":98172533,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596348/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172533"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172533"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172533; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172533]").text(description); $(".js-view-count[data-work-id=98172533]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172533; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172533']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172533, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f47aa4d94d79b02a60d547a121e4ab1c" } } $('.js-work-strip[data-work-id=98172533]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172533,"title":"Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression","translated_title":"","metadata":{"abstract":"Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, λ-carrageenan, or complete Freund\u0026#39;s adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of sucrose into the cerebral hemispheres. Capillary depletion and cerebral blood flow analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Western blot analyses showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the λ-carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172532"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172532/Blood_brain_barrier_tight_junctions_are_altered_during_a_72_h_exposure_to_%CE%BB_carrageenan_induced_inflammatory_pain"><img alt="Research paper thumbnail of Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain" class="work-thumbnail" src="https://attachments.academia-assets.com/99596347/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172532/Blood_brain_barrier_tight_junctions_are_altered_during_a_72_h_exposure_to_%CE%BB_carrageenan_induced_inflammatory_pain">Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functiona...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% λ-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed λ-carrageenan significantly increased brain uptake of [14C]sucrose at 1, 3, 6, and 48 h (139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b631c000a6a83c0d73928184006cf53c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596347,"asset_id":98172532,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596347/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172532"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172532"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172532; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172532]").text(description); $(".js-view-count[data-work-id=98172532]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172532; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172532']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172532, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b631c000a6a83c0d73928184006cf53c" } } $('.js-work-strip[data-work-id=98172532]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172532,"title":"Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain","translated_title":"","metadata":{"abstract":"In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% λ-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed λ-carrageenan significantly increased brain uptake of [14C]sucrose at 1, 3, 6, and 48 h (139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. 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src="https://attachments.academia-assets.com/99596398/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172531/The_blood_brain_barrier_neurovascular_unit_in_health_and_disease">The blood-brain barrier/neurovascular unit in health and disease</a></div><div class="wp-workCard_item"><span>Pharmacological reviews</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and t...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and the central nervous system (CNS). Although originally observed by Paul Ehrlich in 1885, the nature of the BBB was debated well into the 20th century. The anatomical substrate of the BBB is the cerebral microvascular endothelium, which, together with astrocytes, pericytes, neurons, and the extracellular matrix, constitute a &quot;neurovascular unit&quot; that is essential for the health and function of the CNS. Tight junctions (TJ) between endothelial cells of the BBB restrict paracellular diffusion of water-soluble substances from blood to brain. The TJ is an intricate complex of transmembrane (junctional adhesion molecule-1, occludin, and claudins) and cytoplasmic (zonula occludens-1 and -2, cingulin, AF-6, and 7H6) proteins linked to the actin cytoskeleton. The expression and subcellular localization of TJ proteins are modulated by several intrinsic signaling pathways, including those i...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bc106cedc81e2aaf5b54cb1fd0b43a9e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596398,"asset_id":98172531,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596398/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172531"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172531"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172531; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172531]").text(description); $(".js-view-count[data-work-id=98172531]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172531; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172531']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172531, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bc106cedc81e2aaf5b54cb1fd0b43a9e" } } $('.js-work-strip[data-work-id=98172531]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172531,"title":"The blood-brain barrier/neurovascular unit in health and disease","translated_title":"","metadata":{"abstract":"The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and the central nervous system (CNS). 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The expression and subcellular localization of TJ proteins are modulated by several intrinsic signaling pathways, including those 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dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172530"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression"><img alt="Research paper thumbnail of Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression" class="work-thumbnail" src="https://attachments.academia-assets.com/99596408/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression">Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression</a></div><div class="wp-workCard_item"><span>American journal of physiology. Heart and circulatory physiology</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctio...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2 for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB p...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c341e920040c9d7723324af4e655292e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596408,"asset_id":98172530,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596408/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172530"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172530"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172530; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172530]").text(description); $(".js-view-count[data-work-id=98172530]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172530; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172530']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172530, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c341e920040c9d7723324af4e655292e" } } $('.js-work-strip[data-work-id=98172530]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172530,"title":"Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression","translated_title":"","metadata":{"abstract":"Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2 for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB p...","publication_date":{"day":null,"month":null,"year":2003,"errors":{}},"publication_name":"American journal of physiology. Heart and circulatory physiology"},"translated_abstract":"Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2 for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB p...","internal_url":"https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression","translated_internal_url":"","created_at":"2023-03-08T10:40:14.799-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596408,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596408/thumbnails/1.jpg","file_name":"ajpheart.00589.pdf","download_url":"https://www.academia.edu/attachments/99596408/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effects_of_hypoxia_reoxygenation_on_rat.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596408/ajpheart.00589-libre.pdf?1678301417=\u0026response-content-disposition=attachment%3B+filename%3DEffects_of_hypoxia_reoxygenation_on_rat.pdf\u0026Expires=1732985581\u0026Signature=YXTmGSckjbReW04QL5Om-69wE78FyootFlTZPgmvdL~T6rmFzXDr-luGA-ChgfszXbUBGJzjT32cHh4PoAhVwjx7MNgNSNY-KviOz~DrCNY2OPpdhJfI5iG2KLLUvfQO74~p17CR3ao4kQftnNUcc-T4HDbQaire4TZ9ldtTaUM-LTQ00Dy-6SkLyCJD19DGp-aM7VtLbQNRVf3jZ0wG4kyf1ufmhUVx7hxbBbYOQ6htVhRIikhqDaCs0PzNWw6Wb4Kh9I06z0fvipcYt6U5wMhj1-toXdsgMzACDhr18MeXH4SPmp1I9VymFlrQF1q9oVIOw3oDvgTQ0F5NULDFFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression","translated_slug":"","page_count":12,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596408,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596408/thumbnails/1.jpg","file_name":"ajpheart.00589.pdf","download_url":"https://www.academia.edu/attachments/99596408/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effects_of_hypoxia_reoxygenation_on_rat.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596408/ajpheart.00589-libre.pdf?1678301417=\u0026response-content-disposition=attachment%3B+filename%3DEffects_of_hypoxia_reoxygenation_on_rat.pdf\u0026Expires=1732985581\u0026Signature=YXTmGSckjbReW04QL5Om-69wE78FyootFlTZPgmvdL~T6rmFzXDr-luGA-ChgfszXbUBGJzjT32cHh4PoAhVwjx7MNgNSNY-KviOz~DrCNY2OPpdhJfI5iG2KLLUvfQO74~p17CR3ao4kQftnNUcc-T4HDbQaire4TZ9ldtTaUM-LTQ00Dy-6SkLyCJD19DGp-aM7VtLbQNRVf3jZ0wG4kyf1ufmhUVx7hxbBbYOQ6htVhRIikhqDaCs0PzNWw6Wb4Kh9I06z0fvipcYt6U5wMhj1-toXdsgMzACDhr18MeXH4SPmp1I9VymFlrQF1q9oVIOw3oDvgTQ0F5NULDFFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":4594,"name":"Carbon Dioxide","url":"https://www.academia.edu/Documents/in/Carbon_Dioxide"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":67133,"name":"Anoxia","url":"https://www.academia.edu/Documents/in/Anoxia"},{"id":71421,"name":"Capillaries","url":"https://www.academia.edu/Documents/in/Capillaries"},{"id":88321,"name":"Blood Pressure","url":"https://www.academia.edu/Documents/in/Blood_Pressure"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":151448,"name":"American","url":"https://www.academia.edu/Documents/in/American"},{"id":161534,"name":"Perfusion","url":"https://www.academia.edu/Documents/in/Perfusion"},{"id":186234,"name":"Medical Physiology","url":"https://www.academia.edu/Documents/in/Medical_Physiology"},{"id":373249,"name":"Electrolytes","url":"https://www.academia.edu/Documents/in/Electrolytes"},{"id":380825,"name":"Oxygen","url":"https://www.academia.edu/Documents/in/Oxygen"},{"id":466252,"name":"Occludin","url":"https://www.academia.edu/Documents/in/Occludin"},{"id":1371584,"name":"Claudin","url":"https://www.academia.edu/Documents/in/Claudin"},{"id":1665885,"name":"Laser Doppler Flowmetry","url":"https://www.academia.edu/Documents/in/Laser_Doppler_Flowmetry"},{"id":1816594,"name":"Adenosine Triphosphate","url":"https://www.academia.edu/Documents/in/Adenosine_Triphosphate"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172528"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172528/Diclofenac_Attenuates_the_Regional_Effect_of_Carrageenan_on_Blood_Brain_Barrier_Function_and_Cytoarchitecture"><img alt="Research paper thumbnail of Diclofenac Attenuates the Regional Effect of -Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture" class="work-thumbnail" src="https://attachments.academia-assets.com/99596386/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172528/Diclofenac_Attenuates_the_Regional_Effect_of_Carrageenan_on_Blood_Brain_Barrier_Function_and_Cytoarchitecture">Diclofenac Attenuates the Regional Effect of -Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture</a></div><div class="wp-workCard_item"><span>Journal of Pharmacology and Experimental Therapeutics</span><span>, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="98a1e1651e1b7d58cef59c70e5a2cb87" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596386,"asset_id":98172528,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596386/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172528"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172528"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172528; 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Protecting the central nervous system (CNS) from the varying concentrations of ions, proteins, and toxins in the periphery is the dynamically regulated blood-brain barrier (BBB). Recent studies have demonstrated significant modulation of the BBB in a number of diseases and physiological states, including pain. This study expands on previous explorations of acute and chronic pain-induced effects on the function and molecular cytoarchitecture of the barrier. It describes the role of cyclooxygenase (COX) up-regulation by blocking with diclofenac (30 mg/kg, i.p.), and it examines the variation in BBB regulation through various brain regions. Edema and hyperalgesia were induced by-carrageenan and attenuated by the additional administration of diclofenac. Examination of unidirectional [ 14 C]sucrose permeability with multitime in situ perfusion studies demonstrated This work was supported by National Institutes of Health Grants NS 42652 and NS 39592 (to T.P.D.). 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172527"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation"><img alt="Research paper thumbnail of Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation" class="work-thumbnail" src="https://attachments.academia-assets.com/99596390/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation">Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation</a></div><div class="wp-workCard_item"><span>Journal of Cerebral Blood Flow &amp; Metabolism</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercel...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="857092158f21e549152af16622bcd9fa" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596390,"asset_id":98172527,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596390/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172527"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172527"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172527; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172527]").text(description); $(".js-view-count[data-work-id=98172527]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172527; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172527']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172527, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "857092158f21e549152af16622bcd9fa" } } $('.js-work-strip[data-work-id=98172527]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172527,"title":"Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation","translated_title":"","metadata":{"abstract":"The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from ...","publisher":"SAGE Publications","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Journal of Cerebral Blood Flow \u0026amp; Metabolism"},"translated_abstract":"The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. 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_.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a139703b4e1fa09d5bfe544ea2a85229" } } $('.js-work-strip[data-work-id=98172526]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172526,"title":"Nociceptive inhibition prevents inflammatory pain induced changes in the blood–brain barrier","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"Previous studies by our group have shown that peripheral inflammatory insult, using the λcarrageenan inflammatory pain (CIP) model, induced alterations in the molecular and functional properties of the blood-brain barrier (BBB). The question remained whether these changes were mediated via an inflammatory and/or neuronal mechanism. In this study, we investigated the involvement of neuronal input from pain activity on alterations in BBB integrity by peripheral inhibition of nociceptive input. A perineural injection of 0.75% bupivacaine into the right hind leg prior to CIP was used for peripheral nerve block. Upon nerve block, there was a significant decrease in thermal allodynia induced by CIP, but no effect on edema formation 1 h post CIP. BBB permeability was increased 1 h post CIP treatment as determined by in situ brain perfusion of [ 14 C] sucrose; bupivacaine nerve block of CIP caused an attenuation of [ 14 C] sucrose permeability, back to saline control levels. Paralleling the changes in [ 14 C] sucrose permeability, we also report increased expression of three tight junction (TJ) proteins, zonula occluden-1 (ZO-1), occludin and claudin-5 with CIP. Upon bupivacaine nerve block, changes in expression were prevented. These data show that the λ-carrageenan induced changes in [ 14 C] sucrose permeability and protein expression of ZO-1, occludin and claudin-5 are prevented with inhibition of nociceptive input. Therefore, we suggest that nociceptive signaling is in part responsible for the alteration in BBB integrity under CIP.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Brain Research","grobid_abstract_attachment_id":99596392},"translated_abstract":null,"internal_url":"https://www.academia.edu/98172526/Nociceptive_inhibition_prevents_inflammatory_pain_induced_changes_in_the_blood_brain_barrier","translated_internal_url":"","created_at":"2023-03-08T10:40:11.937-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596392,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596392/thumbnails/1.jpg","file_name":"pmc2583462.pdf","download_url":"https://www.academia.edu/attachments/99596392/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nociceptive_inhibition_prevents_inflamma.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596392/pmc2583462-libre.pdf?1678301417=\u0026response-content-disposition=attachment%3B+filename%3DNociceptive_inhibition_prevents_inflamma.pdf\u0026Expires=1732985581\u0026Signature=ILBufykhoGU8~nKaQJsAgbh-xuFVFRbLF8eKf4of6AY0J4AlaN2Nsl4HYp23oUlG759HN3~J4a6XG5RqM4fD0UReIIr~3Mz9SBfN~0AEeA7bVfURHF2OaaEK~xiQtKtyBVslL6ESMhcXG~WvElUSlk2dGuws8zrYbjpde5fxIvyTAHk6mgPv9dA2wgF9dKN-Rw3KTDBKheDrDcA35HRZsHaYDFljGQW1EY~PtISDwuQMyGVaJJNLdcv~0TAt6dybkD8-xUiuAdCe90qS1FEBEx715R2d3ICSurTmIHW4wSIIA4dzJRZeKwa-7ZjF~vziketSitjdZCm8iEe5Esj9Qg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Nociceptive_inhibition_prevents_inflammatory_pain_induced_changes_in_the_blood_brain_barrier","translated_slug":"","page_count":14,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas 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Science","url":"https://www.academia.edu/Documents/in/Cognitive_Science"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":9334,"name":"Inflammation","url":"https://www.academia.edu/Documents/in/Inflammation"},{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":509430,"name":"Nociception","url":"https://www.academia.edu/Documents/in/Nociception"},{"id":561009,"name":"Nerve 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class="work-thumbnail" src="https://attachments.academia-assets.com/99596391/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172525/Nicotine_increases_in_vivo_blood_brain_barrier_permeability_and_alters_cerebral_microvascular_tight_junction_protein_distribution">Nicotine increases in vivo blood–brain barrier permeability and alters cerebral microvascular tight junction protein distribution</a></div><div class="wp-workCard_item"><span>Brain Research</span><span>, 2004</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0e393f4b9f9abd3bd2860f2b64943b83" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596391,"asset_id":98172525,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596391/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172525"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172525"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172525; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172525]").text(description); $(".js-view-count[data-work-id=98172525]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172525; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172525']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172525, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "0e393f4b9f9abd3bd2860f2b64943b83" } } $('.js-work-strip[data-work-id=98172525]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172525,"title":"Nicotine increases in vivo blood–brain barrier permeability and alters cerebral microvascular tight junction protein distribution","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"The blood-brain barrier (BBB) is critical to the health of the central nervous system. The BBB is formed primarily by the presence of tight junctions (TJ) between cerebral microvessel endothelial cells. In light of the known effects of nicotine on endothelial cell biology, the specific effects of nicotine on the in vivo BBB were examined. Using in situ brain perfusion, it was found that continuous administration of nicotine (4.5 mg free based kg À1 d day À1) for 1 and 7 days led to increased permeability of the BBB to [ 14 C]-sucrose without significant changes in its initial volume of distribution. The expression and distribution of the TJ-associated proteins actin, occludin, claudin-1,-3, and-5, and ZO-1 and-2 were analyzed by Western blot and immunofluorescence microscopy. Though no changes in total protein expression were observed, nicotine treatment was associated with altered cellular distribution of ZO-1 and diminished junctional immunoreactivity of claudin-3. It is proposed that nicotine leads to changes in BBB permeability via the modulation of TJ proteins.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Brain Research","grobid_abstract_attachment_id":99596391},"translated_abstract":null,"internal_url":"https://www.academia.edu/98172525/Nicotine_increases_in_vivo_blood_brain_barrier_permeability_and_alters_cerebral_microvascular_tight_junction_protein_distribution","translated_internal_url":"","created_at":"2023-03-08T10:40:10.590-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596391,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596391/thumbnails/1.jpg","file_name":"nicotine.brain.rao.pdf","download_url":"https://www.academia.edu/attachments/99596391/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nicotine_increases_in_vivo_blood_brain_b.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596391/nicotine.brain.rao-libre.pdf?1678301420=\u0026response-content-disposition=attachment%3B+filename%3DNicotine_increases_in_vivo_blood_brain_b.pdf\u0026Expires=1732985581\u0026Signature=WF6c0pt5VUFs5izNWoydDEyvYh3BAN~95ZH35pX0Q85oNZ2uYOSdIWOMQkrhdSaLWgoIOdugGVXdZG6Zyq55c4EQAEcK5c0yN22KB6x1PaYLWg81LDlrpnsBziBo1SN~0wqmlyQvCPsJUMavaUtufvOTr4t8Rr5TiW~FV1Z0vQkB4ffV-iaKWLcjS4um4j441CKmy8Y66cQrXaWOnlGdmRZ93~gfy9A8NzfMYAhWrYVfvheaHFQWGBrSKD~I--c2SvgXktpHOB9nxgpI8xiIS94sTftOrTrX-F3wP7ujhm4WErcOntuP-C2b21~t9K-JCloMn6JsTD8c1FeX0mnUVA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Nicotine_increases_in_vivo_blood_brain_barrier_permeability_and_alters_cerebral_microvascular_tight_junction_protein_distribution","translated_slug":"","page_count":11,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596391,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596391/thumbnails/1.jpg","file_name":"nicotine.brain.rao.pdf","download_url":"https://www.academia.edu/attachments/99596391/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nicotine_increases_in_vivo_blood_brain_b.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596391/nicotine.brain.rao-libre.pdf?1678301420=\u0026response-content-disposition=attachment%3B+filename%3DNicotine_increases_in_vivo_blood_brain_b.pdf\u0026Expires=1732985581\u0026Signature=WF6c0pt5VUFs5izNWoydDEyvYh3BAN~95ZH35pX0Q85oNZ2uYOSdIWOMQkrhdSaLWgoIOdugGVXdZG6Zyq55c4EQAEcK5c0yN22KB6x1PaYLWg81LDlrpnsBziBo1SN~0wqmlyQvCPsJUMavaUtufvOTr4t8Rr5TiW~FV1Z0vQkB4ffV-iaKWLcjS4um4j441CKmy8Y66cQrXaWOnlGdmRZ93~gfy9A8NzfMYAhWrYVfvheaHFQWGBrSKD~I--c2SvgXktpHOB9nxgpI8xiIS94sTftOrTrX-F3wP7ujhm4WErcOntuP-C2b21~t9K-JCloMn6JsTD8c1FeX0mnUVA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":237,"name":"Cognitive Science","url":"https://www.academia.edu/Documents/in/Cognitive_Science"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins"},{"id":13827,"name":"Cell Biology","url":"https://www.academia.edu/Documents/in/Cell_Biology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":78117,"name":"Carbon Isotopes","url":"https://www.academia.edu/Documents/in/Carbon_Isotopes"},{"id":91360,"name":"Nicotine","url":"https://www.academia.edu/Documents/in/Nicotine"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":147195,"name":"Central Nervous 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172522"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172522/Biphasic_cytoarchitecture_and_functional_changes_in_the_BBB_induced_by_chronic_inflammatory_pain"><img alt="Research paper thumbnail of Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain" class="work-thumbnail" src="https://attachments.academia-assets.com/99596404/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172522/Biphasic_cytoarchitecture_and_functional_changes_in_the_BBB_induced_by_chronic_inflammatory_pain">Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain</a></div><div class="wp-workCard_item"><span>Brain Research</span><span>, 2006</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="591c2fb0dbc09d8f62300bd0fce733ca" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596404,"asset_id":98172522,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596404/download_file?st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span 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Inflammatory pain (IP) is a condition underlying several diseases with known BBB perturbations, including stroke, Parkinson's, multiple sclerosis and Alzheimer's. Exploring the underlying pathology of chronic IP, we demonstrated alterations in BBB paracellular permeability with correlating changes in tight junction (TJ) proteins: occludin and claudin-5. The present study examines the IP-induced molecular changes leading to a loss in functional BBB integrity. IP was induced by injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the right hindpaw of female Sprague-Dawley rats. Inflammation and hyperalgesia were confirmed, and BBB paracellular permeability was assessed by in situ brain perfusion of [ 14 C]sucrose (paracellular diffusion marker). The permeability of the BBB was significantly increased at 24 and 72 h post-CFA. Analysis of the TJ proteins, which control the paracellular pathway, demonstrated decreased claudin-5 expression at 24 h, and an increase at 48 and 72 h post-injection. Occludin expression was significantly decreased 72 h post-CFA. Expression of junction adhesion molecule-1 (JAM-1) increased 48 h and decreased by 72 h post-CFA. Confocal microscopy demonstrated continuous expression of both occludin and JAM-1, each co-localizing with ZO-1. The increased claudin-5 expression was not limited to the junction. These results provide evidence that chronic IP causes dramatic alterations in specific cytoarchitectural proteins and demonstrate alterations in molecular properties during CFA, resulting in significant changes in BBB paracellular permeability.","publication_date":{"day":null,"month":null,"year":2006,"errors":{}},"publication_name":"Brain 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172519"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172519/Alterations_in_blood_brain_barrier_ICAM_1_expression_and_brain_microglial_activation_after_%CE%BB_carrageenan_induced_inflammatory_pain"><img alt="Research paper thumbnail of Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain" class="work-thumbnail" src="https://attachments.academia-assets.com/99596341/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172519/Alterations_in_blood_brain_barrier_ICAM_1_expression_and_brain_microglial_activation_after_%CE%BB_carrageenan_induced_inflammatory_pain">Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) per...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow c...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bcb930a763a9d2b2cf9033df08ad798c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596341,"asset_id":98172519,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596341/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172519"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172519"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172519; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172519]").text(description); $(".js-view-count[data-work-id=98172519]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172519; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172519']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172519, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bcb930a763a9d2b2cf9033df08ad798c" } } $('.js-work-strip[data-work-id=98172519]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172519,"title":"Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain","translated_title":"","metadata":{"abstract":"Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow c...","publisher":"American Physiological Society","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"American Journal of Physiology-Heart and Circulatory Physiology"},"translated_abstract":"Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow 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wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172516/Chronic_inflammatory_pain_leads_to_increased_blood_brain_barrier_permeability_and_tight_junction_protein_alterations">Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freund&#39;s adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and infrared paw-withdrawal latency. At 72 h postinjection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [14C]sucrose while rats were under pentobarbital anesthesia demons...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bdd8c84a405a71b6bdf1e9146da12c6b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596335,"asset_id":98172516,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596335/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172516"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172516"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172516; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172516]").text(description); $(".js-view-count[data-work-id=98172516]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172516; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172516']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172516, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bdd8c84a405a71b6bdf1e9146da12c6b" } } $('.js-work-strip[data-work-id=98172516]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172516,"title":"Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations","translated_title":"","metadata":{"abstract":"The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172417"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172417/Transport_Mechanisms_at_the_Blood_Brain_Barrier_and_in_Cellular_Compartments_of_the_Neurovascular_Unit_Focus_on_CNS_Delivery_of_Small_Molecule_Drugs"><img alt="Research paper thumbnail of Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs" class="work-thumbnail" src="https://attachments.academia-assets.com/99596232/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172417/Transport_Mechanisms_at_the_Blood_Brain_Barrier_and_in_Cellular_Compartments_of_the_Neurovascular_Unit_Focus_on_CNS_Delivery_of_Small_Molecule_Drugs">Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Ischemic stroke is a primary origin of morbidity and mortality in the United States and around th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. Indeed, several research projects have attempted to discover new drugs or repurpose existing therapeutics to advance stroke pharmacotherapy. Many of these preclinical stroke studies have reported positive results for neuroprotective agents; however, only one compound (3K3A-activated protein C (3K3A-APC)) has advanced to Phase III clinical trial evaluation. One reason for these many failures is the lack of consideration of transport mechanisms at the blood–brain barrier (BBB) and neurovascular unit (NVU). These endogenous transport processes function as a “gateway” that is a primary determinant of efficacious brain concentrations for centrally acting drugs. Despite the knowledge that some neuroprotective agents (i.e., statins and memantine) are substrates for these endogenous BBB transporters, preclinical stroke studies have largely ignored the role of transporters in CNS drug di...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a1f1e9d7ce5450cc18021997aca0707f" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596232,"asset_id":98172417,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596232/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172417"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172417"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172417; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172417]").text(description); $(".js-view-count[data-work-id=98172417]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172417; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172417']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172417, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a1f1e9d7ce5450cc18021997aca0707f" } } $('.js-work-strip[data-work-id=98172417]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172417,"title":"Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs","translated_title":"","metadata":{"abstract":"Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. 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Despite the knowledge that some neuroprotective agents (i.e., statins and memantine) are substrates for these endogenous BBB transporters, preclinical stroke studies have largely ignored the role of transporters in CNS drug di...","publisher":"MDPI AG","publication_name":"Pharmaceutics"},"translated_abstract":"Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. Indeed, several research projects have attempted to discover new drugs or repurpose existing therapeutics to advance stroke pharmacotherapy. Many of these preclinical stroke studies have reported positive results for neuroprotective agents; however, only one compound (3K3A-activated protein C (3K3A-APC)) has advanced to Phase III clinical trial evaluation. One reason for these many failures is the lack of consideration of transport mechanisms at the blood–brain barrier (BBB) and neurovascular unit (NVU). 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172415"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172415/Blood_Brain_Barrier_Transporters_Opportunities_for_Therapeutic_Development_in_Ischemic_Stroke"><img alt="Research paper thumbnail of Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke" class="work-thumbnail" src="https://attachments.academia-assets.com/99596230/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172415/Blood_Brain_Barrier_Transporters_Opportunities_for_Therapeutic_Development_in_Ischemic_Stroke">Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke</a></div><div class="wp-workCard_item"><span>International Journal of Molecular Sciences</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Globally, stroke is a leading cause of death and long-term disability. Over the past decades, sev...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypep...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c983936999d2091036f46a88661d2c63" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596230,"asset_id":98172415,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596230/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172415"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172415"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172415; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172415]").text(description); $(".js-view-count[data-work-id=98172415]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172415; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172415']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172415, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c983936999d2091036f46a88661d2c63" } } $('.js-work-strip[data-work-id=98172415]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172415,"title":"Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke","translated_title":"","metadata":{"abstract":"Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypep...","publisher":"MDPI AG","publication_name":"International Journal of Molecular Sciences"},"translated_abstract":"Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172413"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172413/High_Dose_Acetaminophen_Alters_the_Integrity_of_the_Blood_Brain_Barrier_and_Leads_to_Increased_CNS_Uptake_of_Codeine_in_Rats"><img alt="Research paper thumbnail of High-Dose Acetaminophen Alters the Integrity of the Blood–Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats" class="work-thumbnail" src="https://attachments.academia-assets.com/99596229/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172413/High_Dose_Acetaminophen_Alters_the_Integrity_of_the_Blood_Brain_Barrier_and_Leads_to_Increased_CNS_Uptake_of_Codeine_in_Rats">High-Dose Acetaminophen Alters the Integrity of the Blood–Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; howeve...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; however, effects of APAP on blood–brain barrier (BBB) integrity are unknown. BBB changes by APAP can have profound consequences for brain delivery of co-administered drugs. To study APAP effects, female Sprague–Dawley rats (12–16 weeks old) were administered vehicle (i.e., 100% dimethyl sulfoxide (DMSO), intraperitoneally (i.p.)) or APAP (80 mg/kg or 500 mg/kg in DMSO, i.p.; equivalent to a 900 mg or 5600 mg daily dose for a 70 kg human subject). BBB permeability was measured via in situ brain perfusion using [14C]sucrose and [3H]codeine, an opioid analgesic drug that is co-administered with APAP (i.e., Tylenol #3). Localization and protein expression of tight junction proteins (i.e., claudin-5, occludin, ZO-1) were studied in rat brain microvessels using Western blot analysis and confocal microscopy, respectively. Paracellular [14C]sucrose “leak” and brain [3H]codeine accumulation were signif...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="05499e226fc55b2bb13ffe6d45f1135d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596229,"asset_id":98172413,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596229/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172413"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172413"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172413; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172413]").text(description); $(".js-view-count[data-work-id=98172413]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172413; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172413']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172413, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "05499e226fc55b2bb13ffe6d45f1135d" } } $('.js-work-strip[data-work-id=98172413]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172413,"title":"High-Dose Acetaminophen Alters the Integrity of the Blood–Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats","translated_title":"","metadata":{"abstract":"The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; however, effects of APAP on blood–brain barrier (BBB) integrity are unknown. BBB changes by APAP can have profound consequences for brain delivery of co-administered drugs. To study APAP effects, female Sprague–Dawley rats (12–16 weeks old) were administered vehicle (i.e., 100% dimethyl sulfoxide (DMSO), intraperitoneally (i.p.)) or APAP (80 mg/kg or 500 mg/kg in DMSO, i.p.; equivalent to a 900 mg or 5600 mg daily dose for a 70 kg human subject). BBB permeability was measured via in situ brain perfusion using [14C]sucrose and [3H]codeine, an opioid analgesic drug that is co-administered with APAP (i.e., Tylenol #3). Localization and protein expression of tight junction proteins (i.e., claudin-5, occludin, ZO-1) were studied in rat brain microvessels using Western blot analysis and confocal microscopy, respectively. Paracellular [14C]sucrose “leak” and brain [3H]codeine accumulation were signif...","publisher":"MDPI AG","publication_name":"Pharmaceutics"},"translated_abstract":"The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; however, effects of APAP on blood–brain barrier (BBB) integrity are unknown. BBB changes by APAP can have profound consequences for brain delivery of co-administered drugs. To study APAP effects, female Sprague–Dawley rats (12–16 weeks old) were administered vehicle (i.e., 100% dimethyl sulfoxide (DMSO), intraperitoneally (i.p.)) or APAP (80 mg/kg or 500 mg/kg in DMSO, i.p.; equivalent to a 900 mg or 5600 mg daily dose for a 70 kg human subject). BBB permeability was measured via in situ brain perfusion using [14C]sucrose and [3H]codeine, an opioid analgesic drug that is co-administered with APAP (i.e., Tylenol #3). Localization and protein expression of tight junction proteins (i.e., claudin-5, occludin, ZO-1) were studied in rat brain microvessels using Western blot analysis and confocal microscopy, respectively. Paracellular [14C]sucrose “leak” and brain [3H]codeine accumulation were signif...","internal_url":"https://www.academia.edu/98172413/High_Dose_Acetaminophen_Alters_the_Integrity_of_the_Blood_Brain_Barrier_and_Leads_to_Increased_CNS_Uptake_of_Codeine_in_Rats","translated_internal_url":"","created_at":"2023-03-08T10:38:22.172-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596229,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596229/thumbnails/1.jpg","file_name":"pdf.pdf","download_url":"https://www.academia.edu/attachments/99596229/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"High_Dose_Acetaminophen_Alters_the_Integ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596229/pdf-libre.pdf?1678301446=\u0026response-content-disposition=attachment%3B+filename%3DHigh_Dose_Acetaminophen_Alters_the_Integ.pdf\u0026Expires=1732985582\u0026Signature=Y7TS~u7QQlWn4Rp8P7gUA5aOrHhNN64UyrAUpFfVF57BSwsylUHNTFv2mti3RCUjQKaLCZ3AFsOAxs-wB-rXoQS9YaNunH5asfW3pQ1UkQoQc3zfLwNuU7jw~oyMYbWY5cZIit0MriOLQfykU~GXVfcMq9sxu-U52oTqXElW4gK8oShY6yIEDeuUrjpsx7XH9MO68O~5JO9QlETGz2KuBP3R3~4-wv9sllXvJsu5HhMg-B~~PZ3VvvjB7-rbvScLrA1CaTMERckZG3Mbl75MLHZNTrIIbtQ~K2gySbbUcJxHJbUt9M7zF4-GRBs-qfkSlVzPeSxYa-0rmUgaRz9t2A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"High_Dose_Acetaminophen_Alters_the_Integrity_of_the_Blood_Brain_Barrier_and_Leads_to_Increased_CNS_Uptake_of_Codeine_in_Rats","translated_slug":"","page_count":15,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596229,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596229/thumbnails/1.jpg","file_name":"pdf.pdf","download_url":"https://www.academia.edu/attachments/99596229/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"High_Dose_Acetaminophen_Alters_the_Integ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596229/pdf-libre.pdf?1678301446=\u0026response-content-disposition=attachment%3B+filename%3DHigh_Dose_Acetaminophen_Alters_the_Integ.pdf\u0026Expires=1732985582\u0026Signature=Y7TS~u7QQlWn4Rp8P7gUA5aOrHhNN64UyrAUpFfVF57BSwsylUHNTFv2mti3RCUjQKaLCZ3AFsOAxs-wB-rXoQS9YaNunH5asfW3pQ1UkQoQc3zfLwNuU7jw~oyMYbWY5cZIit0MriOLQfykU~GXVfcMq9sxu-U52oTqXElW4gK8oShY6yIEDeuUrjpsx7XH9MO68O~5JO9QlETGz2KuBP3R3~4-wv9sllXvJsu5HhMg-B~~PZ3VvvjB7-rbvScLrA1CaTMERckZG3Mbl75MLHZNTrIIbtQ~K2gySbbUcJxHJbUt9M7zF4-GRBs-qfkSlVzPeSxYa-0rmUgaRz9t2A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":41745,"name":"Pharmaceutics","url":"https://www.academia.edu/Documents/in/Pharmaceutics"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":466252,"name":"Occludin","url":"https://www.academia.edu/Documents/in/Occludin"},{"id":724415,"name":"Acetaminophen","url":"https://www.academia.edu/Documents/in/Acetaminophen"},{"id":1619685,"name":"Codeine","url":"https://www.academia.edu/Documents/in/Codeine"}],"urls":[{"id":29609657,"url":"https://www.mdpi.com/1999-4923/14/5/949/pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172411"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172411/Transporter_Mediated_Delivery_of_Small_Molecule_Drugs_to_the_Brain_A_Critical_Mechanism_That_Can_Advance_Therapeutic_Development_for_Ischemic_Stroke"><img alt="Research paper thumbnail of Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke" class="work-thumbnail" src="https://attachments.academia-assets.com/99596228/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172411/Transporter_Mediated_Delivery_of_Small_Molecule_Drugs_to_the_Brain_A_Critical_Mechanism_That_Can_Advance_Therapeutic_Development_for_Ischemic_Stroke">Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Ischemic stroke is the 5th leading cause of death in the United States. Despite significant impro...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from debilitating neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous uptake transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule neuroprotective drug delivery to the brain. Examples of such uptake transporters include organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) and organic cation transporters (OCTs in humans; Octs in rodents). Of particular note, small molecule drugs that have neuroprotective properties are known substrates for these transporters and include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) for OATPs/Oatps and 1-amino-3,5-dimethyladamantane (i.e., memantine) for OCTs/Octs. Here, we revi...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5f56d7bbe6e1e949661ce61a7ac2e95e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596228,"asset_id":98172411,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596228/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172411"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172411"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172411; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172411]").text(description); $(".js-view-count[data-work-id=98172411]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172411; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172411']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172411, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5f56d7bbe6e1e949661ce61a7ac2e95e" } } $('.js-work-strip[data-work-id=98172411]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172411,"title":"Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke","translated_title":"","metadata":{"abstract":"Ischemic stroke is the 5th leading cause of death in the United States. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172410"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172410/Modulation_of_Opioid_Transport_at_the_Blood_Brain_Barrier_by_Altered_ATP_Binding_Cassette_ABC_Transporter_Expression_and_Activity"><img alt="Research paper thumbnail of Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity" class="work-thumbnail" src="https://attachments.academia-assets.com/99596295/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172410/Modulation_of_Opioid_Transport_at_the_Blood_Brain_Barrier_by_Altered_ATP_Binding_Cassette_ABC_Transporter_Expression_and_Activity">Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span><span>, Jan 18, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Opioids are highly effective analgesics that have a serious potential for adverse drug reactions ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. Since the use of opioids has escalated in recent years, it is increasingly important to understand biological mechanisms that can increase the probability of opioid-associated adverse events occurring in patient populations. This is emphasized by the current opioid epidemic in the United States where opioid analgesics are frequently abused and misused. It has been established that the effectiveness of opioids is maximized when these drugs readily access opioid receptors in the central nervous system (CNS). Indeed, opioid delivery to the brain is significantly influenced by the blood-brain barrier (BBB). In particular, ATP-binding cassette (ABC) transporters that are endogenously expressed at the BBB are critical determinants of CNS opioid penetration. In this review, we will discuss current knowledge on the transport of opioid analgesic dru...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1c14ec77bc697f26b56dd2d5f85a554c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596295,"asset_id":98172410,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596295/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172410"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172410"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172410; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172410]").text(description); $(".js-view-count[data-work-id=98172410]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172410; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172410']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172410, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1c14ec77bc697f26b56dd2d5f85a554c" } } $('.js-work-strip[data-work-id=98172410]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172410,"title":"Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity","translated_title":"","metadata":{"abstract":"Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172409"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172409/Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels"><img alt="Research paper thumbnail of Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels" class="work-thumbnail" src="https://attachments.academia-assets.com/99596329/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172409/Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels">Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels</a></div><div class="wp-workCard_item"><span>PloS one</span><span>, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The rates of opioid prescription and use have continued to increase over the last few decades res...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The rates of opioid prescription and use have continued to increase over the last few decades resulting in a greater number of opioid tolerant patients. Treatment of acute pain from surgery and injury is a clinical challenge for these patients. Several pain management strategies including prescribing increased opioids are used clinically with limited success; all currently available strategies have significant limitations. Many opioids are a substrate for p-glycoprotein (p-gp), an efflux transporter at the blood-brain barrier (BBB). Increased p-gp is associated with a decreased central nervous system uptake and analgesic efficacy of morphine. Our laboratory previously found that acute peripheral inflammatory pain (PIP) induces p-gp trafficking from the nucleus to the luminal surface of endothelial cells making up the BBB concomitant with increased p-gp activity and decreased morphine analgesic efficacy. In the current study, we tested whether PIP-induced p-gp trafficking could contr...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dd3c125046acdbbc8a4a7a1b5a8cad15" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596329,"asset_id":98172409,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596329/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172409"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172409"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172409; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172409]").text(description); $(".js-view-count[data-work-id=98172409]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172409; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172409']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172409, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "dd3c125046acdbbc8a4a7a1b5a8cad15" } } $('.js-work-strip[data-work-id=98172409]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172409,"title":"Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels","translated_title":"","metadata":{"abstract":"The rates of opioid prescription and use have continued to increase over the last few decades resulting in a greater number of opioid tolerant patients. Treatment of acute pain from surgery and injury is a clinical challenge for these patients. Several pain management strategies including prescribing increased opioids are used clinically with limited success; all currently available strategies have significant limitations. Many opioids are a substrate for p-glycoprotein (p-gp), an efflux transporter at the blood-brain barrier (BBB). Increased p-gp is associated with a decreased central nervous system uptake and analgesic efficacy of morphine. Our laboratory previously found that acute peripheral inflammatory pain (PIP) induces p-gp trafficking from the nucleus to the luminal surface of endothelial cells making up the BBB concomitant with increased p-gp activity and decreased morphine analgesic efficacy. In the current study, we tested whether PIP-induced p-gp trafficking could contr...","publication_date":{"day":null,"month":null,"year":2018,"errors":{}},"publication_name":"PloS one"},"translated_abstract":"The rates of opioid prescription and use have continued to increase over the last few decades resulting in a greater number of opioid tolerant patients. Treatment of acute pain from surgery and injury is a clinical challenge for these patients. Several pain management strategies including prescribing increased opioids are used clinically with limited success; all currently available strategies have significant limitations. Many opioids are a substrate for p-glycoprotein (p-gp), an efflux transporter at the blood-brain barrier (BBB). Increased p-gp is associated with a decreased central nervous system uptake and analgesic efficacy of morphine. Our laboratory previously found that acute peripheral inflammatory pain (PIP) induces p-gp trafficking from the nucleus to the luminal surface of endothelial cells making up the BBB concomitant with increased p-gp activity and decreased morphine analgesic efficacy. In the current study, we tested whether PIP-induced p-gp trafficking could contr...","internal_url":"https://www.academia.edu/98172409/Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels","translated_internal_url":"","created_at":"2023-03-08T10:38:21.373-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596329,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596329/thumbnails/1.jpg","file_name":"3d1fc087c0ebe4d174b37b94c540e2df5a37.pdf","download_url":"https://www.academia.edu/attachments/99596329/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Chronic_morphine_exposure_potentiates_p.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596329/3d1fc087c0ebe4d174b37b94c540e2df5a37-libre.pdf?1678301627=\u0026response-content-disposition=attachment%3B+filename%3DChronic_morphine_exposure_potentiates_p.pdf\u0026Expires=1732985582\u0026Signature=gjbrfdlzEMe0wnkqHtsZHnfCd6VahJ8OT1~zk7l2dGSh8m-MQPlsbhkd54Cz6s0vIdqgb2yiT7W4ngFxkucUqTZzoL~BIhM~8ln74EPrBjJa00c1yKDze6MYGUcaijKHhOwwse6MLoUnYuUceAZ4o0pM~t6SXem7THKXyTeMdcqnrzrxtEhHPCKtu1P4JoFRucZF29T21Ivj-7opf4DpPgAJdSkNaHwLAHb9gjxqBb9v~j2KVkCprKFFhz0uBLvZXX0-rKxXtXdaUtnj9RRB9CNsYwPt-YpDkkFEL-QvtdnezEuwBLVzVMJSRMOV-ftDwT3b7TdrxHWipIchB4o7Mg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels","translated_slug":"","page_count":16,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596329,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596329/thumbnails/1.jpg","file_name":"3d1fc087c0ebe4d174b37b94c540e2df5a37.pdf","download_url":"https://www.academia.edu/attachments/99596329/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Chronic_morphine_exposure_potentiates_p.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596329/3d1fc087c0ebe4d174b37b94c540e2df5a37-libre.pdf?1678301627=\u0026response-content-disposition=attachment%3B+filename%3DChronic_morphine_exposure_potentiates_p.pdf\u0026Expires=1732985582\u0026Signature=gjbrfdlzEMe0wnkqHtsZHnfCd6VahJ8OT1~zk7l2dGSh8m-MQPlsbhkd54Cz6s0vIdqgb2yiT7W4ngFxkucUqTZzoL~BIhM~8ln74EPrBjJa00c1yKDze6MYGUcaijKHhOwwse6MLoUnYuUceAZ4o0pM~t6SXem7THKXyTeMdcqnrzrxtEhHPCKtu1P4JoFRucZF29T21Ivj-7opf4DpPgAJdSkNaHwLAHb9gjxqBb9v~j2KVkCprKFFhz0uBLvZXX0-rKxXtXdaUtnj9RRB9CNsYwPt-YpDkkFEL-QvtdnezEuwBLVzVMJSRMOV-ftDwT3b7TdrxHWipIchB4o7Mg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience"},{"id":2827,"name":"Mental Health","url":"https://www.academia.edu/Documents/in/Mental_Health"},{"id":2898,"name":"Pain","url":"https://www.academia.edu/Documents/in/Pain"},{"id":17960,"name":"Infectious Diseases","url":"https://www.academia.edu/Documents/in/Infectious_Diseases"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":40165,"name":"Pain Management","url":"https://www.academia.edu/Documents/in/Pain_Management"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":218374,"name":"Morphine","url":"https://www.academia.edu/Documents/in/Morphine"},{"id":220780,"name":"PLoS one","url":"https://www.academia.edu/Documents/in/PLoS_one"},{"id":317801,"name":"Cell nucleus","url":"https://www.academia.edu/Documents/in/Cell_nucleus"},{"id":568887,"name":"Carrageenan","url":"https://www.academia.edu/Documents/in/Carrageenan"},{"id":632073,"name":"CNS","url":"https://www.academia.edu/Documents/in/CNS"},{"id":711582,"name":"Opioid","url":"https://www.academia.edu/Documents/in/Opioid"},{"id":820245,"name":"Analgesic","url":"https://www.academia.edu/Documents/in/Analgesic"},{"id":1310914,"name":"BBB","url":"https://www.academia.edu/Documents/in/BBB"},{"id":1796876,"name":"Microvessels","url":"https://www.academia.edu/Documents/in/Microvessels"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172408"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172408/Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery"><img alt="Research paper thumbnail of Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery" class="work-thumbnail" src="https://attachments.academia-assets.com/99596314/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172408/Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery">Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery</a></div><div class="wp-workCard_item"><span>eNeuro</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expre...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3797c383dd47c818d519ff1c03c63b84" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596314,"asset_id":98172408,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596314/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172408"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172408"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172408; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172408]").text(description); $(".js-view-count[data-work-id=98172408]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172408; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172408']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172408, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3797c383dd47c818d519ff1c03c63b84" } } $('.js-work-strip[data-work-id=98172408]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172408,"title":"Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery","translated_title":"","metadata":{"abstract":"Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expre...","publication_name":"eNeuro"},"translated_abstract":"Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expre...","internal_url":"https://www.academia.edu/98172408/Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery","translated_internal_url":"","created_at":"2023-03-08T10:38:21.254-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596314,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596314/thumbnails/1.jpg","file_name":"ENEURO.0116-18.2018.full.pdf","download_url":"https://www.academia.edu/attachments/99596314/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Loss_of_Blood_Brain_Barrier_Integrity_in.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596314/ENEURO.0116-18.2018.full-libre.pdf?1678301424=\u0026response-content-disposition=attachment%3B+filename%3DLoss_of_Blood_Brain_Barrier_Integrity_in.pdf\u0026Expires=1732985582\u0026Signature=XbJczqBMqvNW4mgTYBSXZJ-eWB6G~M-LyQAKbQAE6NfD5jR~SWAtzb8UHsrYS1mU9dLQ1UEeL1YrXojYShx8sVB5ucD93I2E0r-iMp5ZuTaIxPGmzvax2w7COejgQ59LKsFF4lV5xeqYsjFMcobYQ-OJzmEupbG6aTc9ElztzccF~D6lS3ZY9kwCMXWSxuXkz9tO84IaVF6hF4rwKqqJ0~7RiOkyJdyNW0E3hWbre7SCM55y1UbzJLtUyOx4AIl~HICddDuY67NchKG~j6BdxTT9veDGz3V3OVlxPEMOWsIqHL8VnQiYyzVha22ZGxI5BDzthbxef9WIZAHb1Ggz0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery","translated_slug":"","page_count":14,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596314,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596314/thumbnails/1.jpg","file_name":"ENEURO.0116-18.2018.full.pdf","download_url":"https://www.academia.edu/attachments/99596314/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Loss_of_Blood_Brain_Barrier_Integrity_in.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596314/ENEURO.0116-18.2018.full-libre.pdf?1678301424=\u0026response-content-disposition=attachment%3B+filename%3DLoss_of_Blood_Brain_Barrier_Integrity_in.pdf\u0026Expires=1732985582\u0026Signature=XbJczqBMqvNW4mgTYBSXZJ-eWB6G~M-LyQAKbQAE6NfD5jR~SWAtzb8UHsrYS1mU9dLQ1UEeL1YrXojYShx8sVB5ucD93I2E0r-iMp5ZuTaIxPGmzvax2w7COejgQ59LKsFF4lV5xeqYsjFMcobYQ-OJzmEupbG6aTc9ElztzccF~D6lS3ZY9kwCMXWSxuXkz9tO84IaVF6hF4rwKqqJ0~7RiOkyJdyNW0E3hWbre7SCM55y1UbzJLtUyOx4AIl~HICddDuY67NchKG~j6BdxTT9veDGz3V3OVlxPEMOWsIqHL8VnQiYyzVha22ZGxI5BDzthbxef9WIZAHb1Ggz0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":763475,"name":"Allodynia","url":"https://www.academia.edu/Documents/in/Allodynia"},{"id":1371582,"name":"Tight Junction","url":"https://www.academia.edu/Documents/in/Tight_Junction"},{"id":1798986,"name":"Cortical Spreading Depression","url":"https://www.academia.edu/Documents/in/Cortical_Spreading_Depression"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172407"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172407/Functional_Expression_of_P_glycoprotein_and_Organic_Anion_Transporting_Polypeptides_at_the_Blood_Brain_Barrier_Understanding_Transport_Mechanisms_for_Improved_CNS_Drug_Delivery"><img alt="Research paper thumbnail of Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?" class="work-thumbnail" src="https://attachments.academia-assets.com/99596312/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172407/Functional_Expression_of_P_glycoprotein_and_Organic_Anion_Transporting_Polypeptides_at_the_Blood_Brain_Barrier_Understanding_Transport_Mechanisms_for_Improved_CNS_Drug_Delivery">Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?</a></div><div class="wp-workCard_item"><span>The AAPS journal</span><span>, Jul 26, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="73b4c43609d71ef3a81b4e25cda638f7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596312,"asset_id":98172407,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596312/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172407"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172407"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172407; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172407]").text(description); $(".js-view-count[data-work-id=98172407]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172407; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172407']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172407, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "73b4c43609d71ef3a81b4e25cda638f7" } } $('.js-work-strip[data-work-id=98172407]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172407,"title":"Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?","translated_title":"","metadata":{"abstract":"Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H...","publication_date":{"day":26,"month":7,"year":2017,"errors":{}},"publication_name":"The AAPS journal"},"translated_abstract":"Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H...","internal_url":"https://www.academia.edu/98172407/Functional_Expression_of_P_glycoprotein_and_Organic_Anion_Transporting_Polypeptides_at_the_Blood_Brain_Barrier_Understanding_Transport_Mechanisms_for_Improved_CNS_Drug_Delivery","translated_internal_url":"","created_at":"2023-03-08T10:38:21.102-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596312,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596312/thumbnails/1.jpg","file_name":"ptpmcrender.pdf","download_url":"https://www.academia.edu/attachments/99596312/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Functional_Expression_of_P_glycoprotein.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596312/ptpmcrender-libre.pdf?1678301431=\u0026response-content-disposition=attachment%3B+filename%3DFunctional_Expression_of_P_glycoprotein.pdf\u0026Expires=1732985582\u0026Signature=ErYLmB889cKe-9cz0Ayfeu7ZiftnR06GJ8SF~yJH~viAF3UInqkkk4Cat6h-mzNa3LFduYE~c12pE0m9pcHFwCNXlF73-sucjYyUDzP-xwgnEZjkeX9-wMeheaJ10Om1nDgFobUJzgU3LjGau4Bn84uDevUQOibs2P7trk3Pur9z-WrJyGsD6k7JajZjJU4VGTrZqiEZ8BxBxp7PQ21Qo29SqDDETLn3-3qx3XVmndMhetjMzebc3zdioSnvCr-UafDBU7sp9VGxAd2x3XZA4RYRDXuJgt1Ptrt92bVjPSaWWsTw3qFYKwV2xBowXxC-mBjYTSMrNBfNcBVcwsAHxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Functional_Expression_of_P_glycoprotein_and_Organic_Anion_Transporting_Polypeptides_at_the_Blood_Brain_Barrier_Understanding_Transport_Mechanisms_for_Improved_CNS_Drug_Delivery","translated_slug":"","page_count":19,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596312,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596312/thumbnails/1.jpg","file_name":"ptpmcrender.pdf","download_url":"https://www.academia.edu/attachments/99596312/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Functional_Expression_of_P_glycoprotein.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596312/ptpmcrender-libre.pdf?1678301431=\u0026response-content-disposition=attachment%3B+filename%3DFunctional_Expression_of_P_glycoprotein.pdf\u0026Expires=1732985582\u0026Signature=ErYLmB889cKe-9cz0Ayfeu7ZiftnR06GJ8SF~yJH~viAF3UInqkkk4Cat6h-mzNa3LFduYE~c12pE0m9pcHFwCNXlF73-sucjYyUDzP-xwgnEZjkeX9-wMeheaJ10Om1nDgFobUJzgU3LjGau4Bn84uDevUQOibs2P7trk3Pur9z-WrJyGsD6k7JajZjJU4VGTrZqiEZ8BxBxp7PQ21Qo29SqDDETLn3-3qx3XVmndMhetjMzebc3zdioSnvCr-UafDBU7sp9VGxAd2x3XZA4RYRDXuJgt1Ptrt92bVjPSaWWsTw3qFYKwV2xBowXxC-mBjYTSMrNBfNcBVcwsAHxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":126972,"name":"P-glycoprotein","url":"https://www.academia.edu/Documents/in/P-glycoprotein"},{"id":147195,"name":"Central Nervous System","url":"https://www.academia.edu/Documents/in/Central_Nervous_System"},{"id":159187,"name":"Drug Delivery Systems","url":"https://www.academia.edu/Documents/in/Drug_Delivery_Systems"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="4017844" id="papers"><div class="js-work-strip profile--work_container" data-work-id="98172630"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172630/Effects_of_indomethacin_and_meclofenamate_on_renin_release_and_renal_hemodynamic_function_during_chronic_sodium_depletion_in_conscious_dogs"><img alt="Research paper thumbnail of Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs" class="work-thumbnail" src="https://attachments.academia-assets.com/99596403/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172630/Effects_of_indomethacin_and_meclofenamate_on_renin_release_and_renal_hemodynamic_function_during_chronic_sodium_depletion_in_conscious_dogs">Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs</a></div><div class="wp-workCard_item"><span>Circulation Research</span><span>, 1980</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We studied the control of renin release and renal hemodynamic function by administering prostagla...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. This high level of PRA after blockade of the adre...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="379ff8120487c9a2727cd7a1069e2471" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596403,"asset_id":98172630,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596403/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172630"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172630"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172630; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172630]").text(description); $(".js-view-count[data-work-id=98172630]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172630; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172630']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172630, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "379ff8120487c9a2727cd7a1069e2471" } } $('.js-work-strip[data-work-id=98172630]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172630,"title":"Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs","translated_title":"","metadata":{"abstract":"We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. This high level of PRA after blockade of the adre...","publisher":"Ovid Technologies (Wolters Kluwer Health)","publication_date":{"day":null,"month":null,"year":1980,"errors":{}},"publication_name":"Circulation Research"},"translated_abstract":"We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. This high level of PRA after blockade of the 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Medicine","url":"https://www.academia.edu/Documents/in/Internal_Medicine"},{"id":71294,"name":"Kidney","url":"https://www.academia.edu/Documents/in/Kidney"},{"id":74347,"name":"Hemodynamics","url":"https://www.academia.edu/Documents/in/Hemodynamics"},{"id":160656,"name":"Potassium","url":"https://www.academia.edu/Documents/in/Potassium"},{"id":227354,"name":"Renal Function","url":"https://www.academia.edu/Documents/in/Renal_Function"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences"},{"id":515070,"name":"Circulation","url":"https://www.academia.edu/Documents/in/Circulation"},{"id":637718,"name":"Nervous 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profile--work_container" data-work-id="98172533"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172533/Inflammatory_pain_alters_blood_brain_barrier_permeability_and_tight_junctional_protein_expression"><img alt="Research paper thumbnail of Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression" class="work-thumbnail" src="https://attachments.academia-assets.com/99596348/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172533/Inflammatory_pain_alters_blood_brain_barrier_permeability_and_tight_junctional_protein_expression">Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2001</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, λ-carrageenan, or complete Freund&#39;s adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of sucrose into the cerebral hemispheres. Capillary depletion and cerebral blood flow analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Western blot analyses showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the λ-carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. Claudin-1 protein expression was present at...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f47aa4d94d79b02a60d547a121e4ab1c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596348,"asset_id":98172533,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596348/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172533"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172533"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172533; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172533]").text(description); $(".js-view-count[data-work-id=98172533]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172533; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172533']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172533, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f47aa4d94d79b02a60d547a121e4ab1c" } } $('.js-work-strip[data-work-id=98172533]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172533,"title":"Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression","translated_title":"","metadata":{"abstract":"Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, λ-carrageenan, or complete Freund\u0026#39;s adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of sucrose into the cerebral hemispheres. Capillary depletion and cerebral blood flow analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Western blot analyses showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the λ-carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. Claudin-1 protein expression was present at...","publisher":"American Physiological Society","publication_date":{"day":null,"month":null,"year":2001,"errors":{}},"publication_name":"American Journal of Physiology-Heart and Circulatory Physiology"},"translated_abstract":"Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, λ-carrageenan, or complete Freund\u0026#39;s adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of sucrose into the cerebral hemispheres. Capillary depletion and cerebral blood flow analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Western blot analyses showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the λ-carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172532"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172532/Blood_brain_barrier_tight_junctions_are_altered_during_a_72_h_exposure_to_%CE%BB_carrageenan_induced_inflammatory_pain"><img alt="Research paper thumbnail of Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain" class="work-thumbnail" src="https://attachments.academia-assets.com/99596347/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172532/Blood_brain_barrier_tight_junctions_are_altered_during_a_72_h_exposure_to_%CE%BB_carrageenan_induced_inflammatory_pain">Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functiona...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% λ-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed λ-carrageenan significantly increased brain uptake of [14C]sucrose at 1, 3, 6, and 48 h (139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b631c000a6a83c0d73928184006cf53c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596347,"asset_id":98172532,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596347/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172532"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172532"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172532; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172532]").text(description); $(".js-view-count[data-work-id=98172532]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172532; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172532']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172532, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b631c000a6a83c0d73928184006cf53c" } } $('.js-work-strip[data-work-id=98172532]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172532,"title":"Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain","translated_title":"","metadata":{"abstract":"In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% λ-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed λ-carrageenan significantly increased brain uptake of [14C]sucrose at 1, 3, 6, and 48 h (139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin...","publisher":"American Physiological Society","publication_date":{"day":null,"month":null,"year":2002,"errors":{}},"publication_name":"American Journal of Physiology-Heart and Circulatory Physiology"},"translated_abstract":"In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% λ-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed λ-carrageenan significantly increased brain uptake of [14C]sucrose at 1, 3, 6, and 48 h (139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. 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src="https://attachments.academia-assets.com/99596398/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172531/The_blood_brain_barrier_neurovascular_unit_in_health_and_disease">The blood-brain barrier/neurovascular unit in health and disease</a></div><div class="wp-workCard_item"><span>Pharmacological reviews</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and t...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and the central nervous system (CNS). Although originally observed by Paul Ehrlich in 1885, the nature of the BBB was debated well into the 20th century. The anatomical substrate of the BBB is the cerebral microvascular endothelium, which, together with astrocytes, pericytes, neurons, and the extracellular matrix, constitute a &quot;neurovascular unit&quot; that is essential for the health and function of the CNS. Tight junctions (TJ) between endothelial cells of the BBB restrict paracellular diffusion of water-soluble substances from blood to brain. The TJ is an intricate complex of transmembrane (junctional adhesion molecule-1, occludin, and claudins) and cytoplasmic (zonula occludens-1 and -2, cingulin, AF-6, and 7H6) proteins linked to the actin cytoskeleton. The expression and subcellular localization of TJ proteins are modulated by several intrinsic signaling pathways, including those i...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bc106cedc81e2aaf5b54cb1fd0b43a9e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596398,"asset_id":98172531,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596398/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172531"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172531"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172531; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172531]").text(description); $(".js-view-count[data-work-id=98172531]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172531; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172531']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172531, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bc106cedc81e2aaf5b54cb1fd0b43a9e" } } $('.js-work-strip[data-work-id=98172531]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172531,"title":"The blood-brain barrier/neurovascular unit in health and disease","translated_title":"","metadata":{"abstract":"The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and the central nervous system (CNS). 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dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172530"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression"><img alt="Research paper thumbnail of Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression" class="work-thumbnail" src="https://attachments.academia-assets.com/99596408/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression">Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression</a></div><div class="wp-workCard_item"><span>American journal of physiology. Heart and circulatory physiology</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctio...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2 for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB p...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c341e920040c9d7723324af4e655292e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596408,"asset_id":98172530,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596408/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172530"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172530"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172530; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172530]").text(description); $(".js-view-count[data-work-id=98172530]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172530; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172530']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172530, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c341e920040c9d7723324af4e655292e" } } $('.js-work-strip[data-work-id=98172530]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172530,"title":"Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression","translated_title":"","metadata":{"abstract":"Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. 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Heart and circulatory physiology"},"translated_abstract":"Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2 for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172528"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172528/Diclofenac_Attenuates_the_Regional_Effect_of_Carrageenan_on_Blood_Brain_Barrier_Function_and_Cytoarchitecture"><img alt="Research paper thumbnail of Diclofenac Attenuates the Regional Effect of -Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture" class="work-thumbnail" src="https://attachments.academia-assets.com/99596386/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172528/Diclofenac_Attenuates_the_Regional_Effect_of_Carrageenan_on_Blood_Brain_Barrier_Function_and_Cytoarchitecture">Diclofenac Attenuates the Regional Effect of -Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture</a></div><div class="wp-workCard_item"><span>Journal of Pharmacology and Experimental Therapeutics</span><span>, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="98a1e1651e1b7d58cef59c70e5a2cb87" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596386,"asset_id":98172528,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596386/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172528"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172528"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172528; 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Protecting the central nervous system (CNS) from the varying concentrations of ions, proteins, and toxins in the periphery is the dynamically regulated blood-brain barrier (BBB). Recent studies have demonstrated significant modulation of the BBB in a number of diseases and physiological states, including pain. This study expands on previous explorations of acute and chronic pain-induced effects on the function and molecular cytoarchitecture of the barrier. It describes the role of cyclooxygenase (COX) up-regulation by blocking with diclofenac (30 mg/kg, i.p.), and it examines the variation in BBB regulation through various brain regions. Edema and hyperalgesia were induced by-carrageenan and attenuated by the additional administration of diclofenac. Examination of unidirectional [ 14 C]sucrose permeability with multitime in situ perfusion studies demonstrated This work was supported by National Institutes of Health Grants NS 42652 and NS 39592 (to T.P.D.). Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Journal of Pharmacology and Experimental Therapeutics","grobid_abstract_attachment_id":99596386},"translated_abstract":null,"internal_url":"https://www.academia.edu/98172528/Diclofenac_Attenuates_the_Regional_Effect_of_Carrageenan_on_Blood_Brain_Barrier_Function_and_Cytoarchitecture","translated_internal_url":"","created_at":"2023-03-08T10:40:13.078-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596386,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596386/thumbnails/1.jpg","file_name":"665.full.pdf","download_url":"https://www.academia.edu/attachments/99596386/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Diclofenac_Attenuates_the_Regional_Effec.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596386/665.full-libre.pdf?1678301417=\u0026response-content-disposition=attachment%3B+filename%3DDiclofenac_Attenuates_the_Regional_Effec.pdf\u0026Expires=1732985581\u0026Signature=MSW6LG9Mb6-bp9EYHa2HM-3tfe-Jib2W6ZSWF-Nk9Zlb3kGBnTEGoiI1VKpipibjzAHHJax-Q2A5dxcADnYKNzEYoAnWCPBSbGooSBjGftjnkd~VTV7L5dUVj9H2tCvlF64TYe46wH~qkY~OgRbK0tQk4L-jnjFzouIBbqn5QaQ-UWEIIiAzt0KCfGNKjh7ifKeOiJl3Y2mRbzYO1pT8PNWUVxt7GDtn3LBoIavl8Zq6BVYnSMR1c09PYtKdzL1CYxebDDe7p6IsaJOAeu~q42UAfQFNlMK7Kg7hMM6xRqeTcLjZqxuSjDe0NcUvRFc6A6hhwCP3exG7Cj-HXl40qQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Diclofenac_Attenuates_the_Regional_Effect_of_Carrageenan_on_Blood_Brain_Barrier_Function_and_Cytoarchitecture","translated_slug":"","page_count":9,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596386,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596386/thumbnails/1.jpg","file_name":"665.full.pdf","download_url":"https://www.academia.edu/attachments/99596386/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Diclofenac_Attenuates_the_Regional_Effec.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596386/665.full-libre.pdf?1678301417=\u0026response-content-disposition=attachment%3B+filename%3DDiclofenac_Attenuates_the_Regional_Effec.pdf\u0026Expires=1732985581\u0026Signature=MSW6LG9Mb6-bp9EYHa2HM-3tfe-Jib2W6ZSWF-Nk9Zlb3kGBnTEGoiI1VKpipibjzAHHJax-Q2A5dxcADnYKNzEYoAnWCPBSbGooSBjGftjnkd~VTV7L5dUVj9H2tCvlF64TYe46wH~qkY~OgRbK0tQk4L-jnjFzouIBbqn5QaQ-UWEIIiAzt0KCfGNKjh7ifKeOiJl3Y2mRbzYO1pT8PNWUVxt7GDtn3LBoIavl8Zq6BVYnSMR1c09PYtKdzL1CYxebDDe7p6IsaJOAeu~q42UAfQFNlMK7Kg7hMM6xRqeTcLjZqxuSjDe0NcUvRFc6A6hhwCP3exG7Cj-HXl40qQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":2898,"name":"Pain","url":"https://www.academia.edu/Documents/in/Pain"},{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":99422,"name":"Brainstem","url":"https://www.academia.edu/Documents/in/Brainstem"},{"id":147195,"name":"Central Nervous System","url":"https://www.academia.edu/Documents/in/Central_Nervous_System"},{"id":162196,"name":"Sucrose","url":"https://www.academia.edu/Documents/in/Sucrose"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":382481,"name":"Edema","url":"https://www.academia.edu/Documents/in/Edema"},{"id":568887,"name":"Carrageenan","url":"https://www.academia.edu/Documents/in/Carrageenan"},{"id":569980,"name":"Diclofenac","url":"https://www.academia.edu/Documents/in/Diclofenac"},{"id":1792403,"name":"Tight Junctions","url":"https://www.academia.edu/Documents/in/Tight_Junctions"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172527"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation"><img alt="Research paper thumbnail of Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation" class="work-thumbnail" src="https://attachments.academia-assets.com/99596390/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation">Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation</a></div><div class="wp-workCard_item"><span>Journal of Cerebral Blood Flow &amp; Metabolism</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercel...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="857092158f21e549152af16622bcd9fa" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596390,"asset_id":98172527,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596390/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172527"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172527"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172527; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172527]").text(description); $(".js-view-count[data-work-id=98172527]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172527; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172527']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172527, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "857092158f21e549152af16622bcd9fa" } } $('.js-work-strip[data-work-id=98172527]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172527,"title":"Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation","translated_title":"","metadata":{"abstract":"The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from ...","publisher":"SAGE Publications","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Journal of Cerebral Blood Flow \u0026amp; Metabolism"},"translated_abstract":"The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172526"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172526/Nociceptive_inhibition_prevents_inflammatory_pain_induced_changes_in_the_blood_brain_barrier"><img alt="Research paper thumbnail of Nociceptive inhibition prevents inflammatory pain induced changes in the blood–brain barrier" class="work-thumbnail" src="https://attachments.academia-assets.com/99596392/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172526/Nociceptive_inhibition_prevents_inflammatory_pain_induced_changes_in_the_blood_brain_barrier">Nociceptive inhibition prevents inflammatory pain induced changes in the blood–brain barrier</a></div><div class="wp-workCard_item"><span>Brain Research</span><span>, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a139703b4e1fa09d5bfe544ea2a85229" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596392,"asset_id":98172526,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596392/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172526"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172526"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172526; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172526]").text(description); $(".js-view-count[data-work-id=98172526]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 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_.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a139703b4e1fa09d5bfe544ea2a85229" } } $('.js-work-strip[data-work-id=98172526]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172526,"title":"Nociceptive inhibition prevents inflammatory pain induced changes in the blood–brain barrier","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"Previous studies by our group have shown that peripheral inflammatory insult, using the λcarrageenan inflammatory pain (CIP) model, induced alterations in the molecular and functional properties of the blood-brain barrier (BBB). The question remained whether these changes were mediated via an inflammatory and/or neuronal mechanism. In this study, we investigated the involvement of neuronal input from pain activity on alterations in BBB integrity by peripheral inhibition of nociceptive input. A perineural injection of 0.75% bupivacaine into the right hind leg prior to CIP was used for peripheral nerve block. Upon nerve block, there was a significant decrease in thermal allodynia induced by CIP, but no effect on edema formation 1 h post CIP. BBB permeability was increased 1 h post CIP treatment as determined by in situ brain perfusion of [ 14 C] sucrose; bupivacaine nerve block of CIP caused an attenuation of [ 14 C] sucrose permeability, back to saline control levels. Paralleling the changes in [ 14 C] sucrose permeability, we also report increased expression of three tight junction (TJ) proteins, zonula occluden-1 (ZO-1), occludin and claudin-5 with CIP. Upon bupivacaine nerve block, changes in expression were prevented. These data show that the λ-carrageenan induced changes in [ 14 C] sucrose permeability and protein expression of ZO-1, occludin and claudin-5 are prevented with inhibition of nociceptive input. Therefore, we suggest that nociceptive signaling is in part responsible for the alteration in BBB integrity under CIP.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Brain Research","grobid_abstract_attachment_id":99596392},"translated_abstract":null,"internal_url":"https://www.academia.edu/98172526/Nociceptive_inhibition_prevents_inflammatory_pain_induced_changes_in_the_blood_brain_barrier","translated_internal_url":"","created_at":"2023-03-08T10:40:11.937-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596392,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596392/thumbnails/1.jpg","file_name":"pmc2583462.pdf","download_url":"https://www.academia.edu/attachments/99596392/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nociceptive_inhibition_prevents_inflamma.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596392/pmc2583462-libre.pdf?1678301417=\u0026response-content-disposition=attachment%3B+filename%3DNociceptive_inhibition_prevents_inflamma.pdf\u0026Expires=1732985581\u0026Signature=ILBufykhoGU8~nKaQJsAgbh-xuFVFRbLF8eKf4of6AY0J4AlaN2Nsl4HYp23oUlG759HN3~J4a6XG5RqM4fD0UReIIr~3Mz9SBfN~0AEeA7bVfURHF2OaaEK~xiQtKtyBVslL6ESMhcXG~WvElUSlk2dGuws8zrYbjpde5fxIvyTAHk6mgPv9dA2wgF9dKN-Rw3KTDBKheDrDcA35HRZsHaYDFljGQW1EY~PtISDwuQMyGVaJJNLdcv~0TAt6dybkD8-xUiuAdCe90qS1FEBEx715R2d3ICSurTmIHW4wSIIA4dzJRZeKwa-7ZjF~vziketSitjdZCm8iEe5Esj9Qg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Nociceptive_inhibition_prevents_inflammatory_pain_induced_changes_in_the_blood_brain_barrier","translated_slug":"","page_count":14,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas 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Science","url":"https://www.academia.edu/Documents/in/Cognitive_Science"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":9334,"name":"Inflammation","url":"https://www.academia.edu/Documents/in/Inflammation"},{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":509430,"name":"Nociception","url":"https://www.academia.edu/Documents/in/Nociception"},{"id":561009,"name":"Nerve Block","url":"https://www.academia.edu/Documents/in/Nerve_Block"},{"id":568887,"name":"Carrageenan","url":"https://www.academia.edu/Documents/in/Carrageenan"},{"id":763475,"name":"Allodynia","url":"https://www.academia.edu/Documents/in/Allodynia"},{"id":1239755,"name":"Neurosciences","url":"https://www.academia.edu/Documents/in/Neurosciences"},{"id":1361128,"name":"Inflammatory Pain","url":"https://www.academia.edu/Documents/in/Inflammatory_Pain"},{"id":1363401,"name":"Brain Edema","url":"https://www.academia.edu/Documents/in/Brain_Edema"},{"id":1371584,"name":"Claudin","url":"https://www.academia.edu/Documents/in/Claudin"},{"id":1446320,"name":"Hyperalgesia","url":"https://www.academia.edu/Documents/in/Hyperalgesia"},{"id":1787892,"name":"Nociceptors","url":"https://www.academia.edu/Documents/in/Nociceptors"},{"id":2045377,"name":"Functional Properties","url":"https://www.academia.edu/Documents/in/Functional_Properties"},{"id":2560488,"name":"Bupivacaine","url":"https://www.academia.edu/Documents/in/Bupivacaine"}],"urls":[{"id":29609713,"url":"https://api.elsevier.com/content/article/PII:S0006899308011669?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172525"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172525/Nicotine_increases_in_vivo_blood_brain_barrier_permeability_and_alters_cerebral_microvascular_tight_junction_protein_distribution"><img alt="Research paper thumbnail of Nicotine increases in vivo blood–brain barrier permeability and alters cerebral microvascular tight junction protein distribution" class="work-thumbnail" src="https://attachments.academia-assets.com/99596391/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172525/Nicotine_increases_in_vivo_blood_brain_barrier_permeability_and_alters_cerebral_microvascular_tight_junction_protein_distribution">Nicotine increases in vivo blood–brain barrier permeability and alters cerebral microvascular tight junction protein distribution</a></div><div class="wp-workCard_item"><span>Brain Research</span><span>, 2004</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0e393f4b9f9abd3bd2860f2b64943b83" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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BV","grobid_abstract":"The blood-brain barrier (BBB) is critical to the health of the central nervous system. The BBB is formed primarily by the presence of tight junctions (TJ) between cerebral microvessel endothelial cells. In light of the known effects of nicotine on endothelial cell biology, the specific effects of nicotine on the in vivo BBB were examined. Using in situ brain perfusion, it was found that continuous administration of nicotine (4.5 mg free based kg À1 d day À1) for 1 and 7 days led to increased permeability of the BBB to [ 14 C]-sucrose without significant changes in its initial volume of distribution. The expression and distribution of the TJ-associated proteins actin, occludin, claudin-1,-3, and-5, and ZO-1 and-2 were analyzed by Western blot and immunofluorescence microscopy. Though no changes in total protein expression were observed, nicotine treatment was associated with altered cellular distribution of ZO-1 and diminished junctional immunoreactivity of claudin-3. It is proposed that nicotine leads to changes in BBB permeability via the modulation of TJ proteins.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Brain 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172522"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172522/Biphasic_cytoarchitecture_and_functional_changes_in_the_BBB_induced_by_chronic_inflammatory_pain"><img alt="Research paper thumbnail of Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain" class="work-thumbnail" src="https://attachments.academia-assets.com/99596404/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172522/Biphasic_cytoarchitecture_and_functional_changes_in_the_BBB_induced_by_chronic_inflammatory_pain">Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain</a></div><div class="wp-workCard_item"><span>Brain Research</span><span>, 2006</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="591c2fb0dbc09d8f62300bd0fce733ca" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596404,"asset_id":98172522,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596404/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4MSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172522"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172522"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172522; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172522]").text(description); $(".js-view-count[data-work-id=98172522]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 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_.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "591c2fb0dbc09d8f62300bd0fce733ca" } } $('.js-work-strip[data-work-id=98172522]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172522,"title":"Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"The blood-brain barrier (BBB) is a dynamic system which maintains brain homeostasis and limits CNS penetration via interactions of transmembrane and intracellular proteins. Inflammatory pain (IP) is a condition underlying several diseases with known BBB perturbations, including stroke, Parkinson's, multiple sclerosis and Alzheimer's. Exploring the underlying pathology of chronic IP, we demonstrated alterations in BBB paracellular permeability with correlating changes in tight junction (TJ) proteins: occludin and claudin-5. The present study examines the IP-induced molecular changes leading to a loss in functional BBB integrity. IP was induced by injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the right hindpaw of female Sprague-Dawley rats. Inflammation and hyperalgesia were confirmed, and BBB paracellular permeability was assessed by in situ brain perfusion of [ 14 C]sucrose (paracellular diffusion marker). The permeability of the BBB was significantly increased at 24 and 72 h post-CFA. Analysis of the TJ proteins, which control the paracellular pathway, demonstrated decreased claudin-5 expression at 24 h, and an increase at 48 and 72 h post-injection. Occludin expression was significantly decreased 72 h post-CFA. Expression of junction adhesion molecule-1 (JAM-1) increased 48 h and decreased by 72 h post-CFA. Confocal microscopy demonstrated continuous expression of both occludin and JAM-1, each co-localizing with ZO-1. The increased claudin-5 expression was not limited to the junction. These results provide evidence that chronic IP causes dramatic alterations in specific cytoarchitectural proteins and demonstrate alterations in molecular properties during CFA, resulting in significant changes in BBB paracellular permeability.","publication_date":{"day":null,"month":null,"year":2006,"errors":{}},"publication_name":"Brain 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172519"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172519/Alterations_in_blood_brain_barrier_ICAM_1_expression_and_brain_microglial_activation_after_%CE%BB_carrageenan_induced_inflammatory_pain"><img alt="Research paper thumbnail of Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain" class="work-thumbnail" src="https://attachments.academia-assets.com/99596341/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172519/Alterations_in_blood_brain_barrier_ICAM_1_expression_and_brain_microglial_activation_after_%CE%BB_carrageenan_induced_inflammatory_pain">Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) per...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow c...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bcb930a763a9d2b2cf9033df08ad798c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596341,"asset_id":98172519,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596341/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172519"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172519"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172519; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172519]").text(description); $(".js-view-count[data-work-id=98172519]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172519; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172519']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172519, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bcb930a763a9d2b2cf9033df08ad798c" } } $('.js-work-strip[data-work-id=98172519]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172519,"title":"Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain","translated_title":"","metadata":{"abstract":"Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. 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wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172516/Chronic_inflammatory_pain_leads_to_increased_blood_brain_barrier_permeability_and_tight_junction_protein_alterations">Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations</a></div><div class="wp-workCard_item"><span>American Journal of Physiology-Heart and Circulatory Physiology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freund&#39;s adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and infrared paw-withdrawal latency. At 72 h postinjection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [14C]sucrose while rats were under pentobarbital anesthesia demons...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bdd8c84a405a71b6bdf1e9146da12c6b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596335,"asset_id":98172516,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596335/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172516"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172516"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172516; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172516]").text(description); $(".js-view-count[data-work-id=98172516]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172516; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172516']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172516, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bdd8c84a405a71b6bdf1e9146da12c6b" } } $('.js-work-strip[data-work-id=98172516]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172516,"title":"Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations","translated_title":"","metadata":{"abstract":"The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freund\u0026#39;s adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and infrared paw-withdrawal latency. At 72 h postinjection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [14C]sucrose while rats were under pentobarbital anesthesia demons...","publisher":"American Physiological Society","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"American Journal of Physiology-Heart and Circulatory Physiology"},"translated_abstract":"The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freund\u0026#39;s adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and infrared paw-withdrawal latency. At 72 h postinjection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [14C]sucrose while rats were under pentobarbital anesthesia demons...","internal_url":"https://www.academia.edu/98172516/Chronic_inflammatory_pain_leads_to_increased_blood_brain_barrier_permeability_and_tight_junction_protein_alterations","translated_internal_url":"","created_at":"2023-03-08T10:40:01.799-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596335,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596335/thumbnails/1.jpg","file_name":"ajpheart.01288.pdf","download_url":"https://www.academia.edu/attachments/99596335/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Chronic_inflammatory_pain_leads_to_incre.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596335/ajpheart.01288-libre.pdf?1678301421=\u0026response-content-disposition=attachment%3B+filename%3DChronic_inflammatory_pain_leads_to_incre.pdf\u0026Expires=1732985582\u0026Signature=hCPyE-uIJkO8TwEzdmZrWbu~2IsTE4-5-nnrMr1251DVUxpXN1mh2mkfBdF0iR5IiCloN8vWwcE9jmh6YqMLe5~Vd3WL1gaFcGpVv-ssiYV9OzXaarSA14Nr6feerjS3MHwEAhswV5j-lNAOdx9k8wRCNCobjTzroHpJkphgSByQZz4JeZLFxstqNigdE67CyrQJ0ApcXt7tHpFATjRFn3N4TJxoNVYjWHeKD~wxi55yI0uIto9bzKSNuOlFsvPtg7TjMuNm4u-cnkvk7DemLEPbZU2FRGNveMwqdHq4TdncGS8i9-0XUyEAqrIZyDPQN9YcdU9TH1ciiqyP9uRWng__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Chronic_inflammatory_pain_leads_to_increased_blood_brain_barrier_permeability_and_tight_junction_protein_alterations","translated_slug":"","page_count":6,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596335,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596335/thumbnails/1.jpg","file_name":"ajpheart.01288.pdf","download_url":"https://www.academia.edu/attachments/99596335/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Chronic_inflammatory_pain_leads_to_incre.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596335/ajpheart.01288-libre.pdf?1678301421=\u0026response-content-disposition=attachment%3B+filename%3DChronic_inflammatory_pain_leads_to_incre.pdf\u0026Expires=1732985582\u0026Signature=hCPyE-uIJkO8TwEzdmZrWbu~2IsTE4-5-nnrMr1251DVUxpXN1mh2mkfBdF0iR5IiCloN8vWwcE9jmh6YqMLe5~Vd3WL1gaFcGpVv-ssiYV9OzXaarSA14Nr6feerjS3MHwEAhswV5j-lNAOdx9k8wRCNCobjTzroHpJkphgSByQZz4JeZLFxstqNigdE67CyrQJ0ApcXt7tHpFATjRFn3N4TJxoNVYjWHeKD~wxi55yI0uIto9bzKSNuOlFsvPtg7TjMuNm4u-cnkvk7DemLEPbZU2FRGNveMwqdHq4TdncGS8i9-0XUyEAqrIZyDPQN9YcdU9TH1ciiqyP9uRWng__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":9334,"name":"Inflammation","url":"https://www.academia.edu/Documents/in/Inflammation"},{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":83315,"name":"Diffusion","url":"https://www.academia.edu/Documents/in/Diffusion"},{"id":88321,"name":"Blood Pressure","url":"https://www.academia.edu/Documents/in/Blood_Pressure"},{"id":97269,"name":"Chronic Disease","url":"https://www.academia.edu/Documents/in/Chronic_Disease"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":151448,"name":"American","url":"https://www.academia.edu/Documents/in/American"},{"id":186234,"name":"Medical Physiology","url":"https://www.academia.edu/Documents/in/Medical_Physiology"},{"id":213812,"name":"Difusion","url":"https://www.academia.edu/Documents/in/Difusion"},{"id":379889,"name":"Homeostasis","url":"https://www.academia.edu/Documents/in/Homeostasis"},{"id":382481,"name":"Edema","url":"https://www.academia.edu/Documents/in/Edema"},{"id":449523,"name":"Foot","url":"https://www.academia.edu/Documents/in/Foot"},{"id":466252,"name":"Occludin","url":"https://www.academia.edu/Documents/in/Occludin"},{"id":1371584,"name":"Claudin","url":"https://www.academia.edu/Documents/in/Claudin"},{"id":1446320,"name":"Hyperalgesia","url":"https://www.academia.edu/Documents/in/Hyperalgesia"},{"id":1757315,"name":"Injections","url":"https://www.academia.edu/Documents/in/Injections"}],"urls":[{"id":29609706,"url":"https://www.physiology.org/doi/pdf/10.1152/ajpheart.01288.2004"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172417"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172417/Transport_Mechanisms_at_the_Blood_Brain_Barrier_and_in_Cellular_Compartments_of_the_Neurovascular_Unit_Focus_on_CNS_Delivery_of_Small_Molecule_Drugs"><img alt="Research paper thumbnail of Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs" class="work-thumbnail" src="https://attachments.academia-assets.com/99596232/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172417/Transport_Mechanisms_at_the_Blood_Brain_Barrier_and_in_Cellular_Compartments_of_the_Neurovascular_Unit_Focus_on_CNS_Delivery_of_Small_Molecule_Drugs">Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Ischemic stroke is a primary origin of morbidity and mortality in the United States and around th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. Indeed, several research projects have attempted to discover new drugs or repurpose existing therapeutics to advance stroke pharmacotherapy. Many of these preclinical stroke studies have reported positive results for neuroprotective agents; however, only one compound (3K3A-activated protein C (3K3A-APC)) has advanced to Phase III clinical trial evaluation. One reason for these many failures is the lack of consideration of transport mechanisms at the blood–brain barrier (BBB) and neurovascular unit (NVU). These endogenous transport processes function as a “gateway” that is a primary determinant of efficacious brain concentrations for centrally acting drugs. Despite the knowledge that some neuroprotective agents (i.e., statins and memantine) are substrates for these endogenous BBB transporters, preclinical stroke studies have largely ignored the role of transporters in CNS drug di...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a1f1e9d7ce5450cc18021997aca0707f" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596232,"asset_id":98172417,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596232/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172417"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172417"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172417; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172417]").text(description); $(".js-view-count[data-work-id=98172417]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172417; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172417']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172417, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a1f1e9d7ce5450cc18021997aca0707f" } } $('.js-work-strip[data-work-id=98172417]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172417,"title":"Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs","translated_title":"","metadata":{"abstract":"Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. 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Despite the knowledge that some neuroprotective agents (i.e., statins and memantine) are substrates for these endogenous BBB transporters, preclinical stroke studies have largely ignored the role of transporters in CNS drug di...","publisher":"MDPI AG","publication_name":"Pharmaceutics"},"translated_abstract":"Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. Indeed, several research projects have attempted to discover new drugs or repurpose existing therapeutics to advance stroke pharmacotherapy. Many of these preclinical stroke studies have reported positive results for neuroprotective agents; however, only one compound (3K3A-activated protein C (3K3A-APC)) has advanced to Phase III clinical trial evaluation. One reason for these many failures is the lack of consideration of transport mechanisms at the blood–brain barrier (BBB) and neurovascular unit (NVU). 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172415"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172415/Blood_Brain_Barrier_Transporters_Opportunities_for_Therapeutic_Development_in_Ischemic_Stroke"><img alt="Research paper thumbnail of Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke" class="work-thumbnail" src="https://attachments.academia-assets.com/99596230/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172415/Blood_Brain_Barrier_Transporters_Opportunities_for_Therapeutic_Development_in_Ischemic_Stroke">Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke</a></div><div class="wp-workCard_item"><span>International Journal of Molecular Sciences</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Globally, stroke is a leading cause of death and long-term disability. Over the past decades, sev...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172413"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172413/High_Dose_Acetaminophen_Alters_the_Integrity_of_the_Blood_Brain_Barrier_and_Leads_to_Increased_CNS_Uptake_of_Codeine_in_Rats"><img alt="Research paper thumbnail of High-Dose Acetaminophen Alters the Integrity of the Blood–Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats" class="work-thumbnail" src="https://attachments.academia-assets.com/99596229/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172413/High_Dose_Acetaminophen_Alters_the_Integrity_of_the_Blood_Brain_Barrier_and_Leads_to_Increased_CNS_Uptake_of_Codeine_in_Rats">High-Dose Acetaminophen Alters the Integrity of the Blood–Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; howeve...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; however, effects of APAP on blood–brain barrier (BBB) integrity are unknown. BBB changes by APAP can have profound consequences for brain delivery of co-administered drugs. To study APAP effects, female Sprague–Dawley rats (12–16 weeks old) were administered vehicle (i.e., 100% dimethyl sulfoxide (DMSO), intraperitoneally (i.p.)) or APAP (80 mg/kg or 500 mg/kg in DMSO, i.p.; equivalent to a 900 mg or 5600 mg daily dose for a 70 kg human subject). BBB permeability was measured via in situ brain perfusion using [14C]sucrose and [3H]codeine, an opioid analgesic drug that is co-administered with APAP (i.e., Tylenol #3). Localization and protein expression of tight junction proteins (i.e., claudin-5, occludin, ZO-1) were studied in rat brain microvessels using Western blot analysis and confocal microscopy, respectively. Paracellular [14C]sucrose “leak” and brain [3H]codeine accumulation were signif...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="05499e226fc55b2bb13ffe6d45f1135d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596229,"asset_id":98172413,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596229/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172413"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172413"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172413; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172413]").text(description); $(".js-view-count[data-work-id=98172413]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172413; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172413']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172413, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "05499e226fc55b2bb13ffe6d45f1135d" } } $('.js-work-strip[data-work-id=98172413]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172413,"title":"High-Dose Acetaminophen Alters the Integrity of the Blood–Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats","translated_title":"","metadata":{"abstract":"The consumption of acetaminophen (APAP) can induce neurological changes in human subjects; however, effects of APAP on blood–brain barrier (BBB) integrity are unknown. BBB changes by APAP can have profound consequences for brain delivery of co-administered drugs. To study APAP effects, female Sprague–Dawley rats (12–16 weeks old) were administered vehicle (i.e., 100% dimethyl sulfoxide (DMSO), intraperitoneally (i.p.)) or APAP (80 mg/kg or 500 mg/kg in DMSO, i.p.; equivalent to a 900 mg or 5600 mg daily dose for a 70 kg human subject). BBB permeability was measured via in situ brain perfusion using [14C]sucrose and [3H]codeine, an opioid analgesic drug that is co-administered with APAP (i.e., Tylenol #3). Localization and protein expression of tight junction proteins (i.e., claudin-5, occludin, ZO-1) were studied in rat brain microvessels using Western blot analysis and confocal microscopy, respectively. 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Localization and protein expression of tight junction proteins (i.e., claudin-5, occludin, ZO-1) were studied in rat brain microvessels using Western blot analysis and confocal microscopy, respectively. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172411"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172411/Transporter_Mediated_Delivery_of_Small_Molecule_Drugs_to_the_Brain_A_Critical_Mechanism_That_Can_Advance_Therapeutic_Development_for_Ischemic_Stroke"><img alt="Research paper thumbnail of Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke" class="work-thumbnail" src="https://attachments.academia-assets.com/99596228/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172411/Transporter_Mediated_Delivery_of_Small_Molecule_Drugs_to_the_Brain_A_Critical_Mechanism_That_Can_Advance_Therapeutic_Development_for_Ischemic_Stroke">Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Ischemic stroke is the 5th leading cause of death in the United States. Despite significant impro...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from debilitating neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous uptake transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule neuroprotective drug delivery to the brain. Examples of such uptake transporters include organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) and organic cation transporters (OCTs in humans; Octs in rodents). Of particular note, small molecule drugs that have neuroprotective properties are known substrates for these transporters and include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) for OATPs/Oatps and 1-amino-3,5-dimethyladamantane (i.e., memantine) for OCTs/Octs. Here, we revi...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5f56d7bbe6e1e949661ce61a7ac2e95e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596228,"asset_id":98172411,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596228/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172411"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172411"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172411; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172411]").text(description); $(".js-view-count[data-work-id=98172411]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172411; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172411']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172411, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5f56d7bbe6e1e949661ce61a7ac2e95e" } } $('.js-work-strip[data-work-id=98172411]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172411,"title":"Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke","translated_title":"","metadata":{"abstract":"Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from debilitating neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous uptake transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule neuroprotective drug delivery to the brain. Examples of such uptake transporters include organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) and organic cation transporters (OCTs in humans; Octs in rodents). Of particular note, small molecule drugs that have neuroprotective properties are known substrates for these transporters and include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) for OATPs/Oatps and 1-amino-3,5-dimethyladamantane (i.e., memantine) for OCTs/Octs. Here, we revi...","publisher":"MDPI AG","publication_date":{"day":null,"month":null,"year":2020,"errors":{}},"publication_name":"Pharmaceutics"},"translated_abstract":"Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from debilitating neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous uptake transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule neuroprotective drug delivery to the brain. Examples of such uptake transporters include organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) and organic cation transporters (OCTs in humans; Octs in rodents). 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}); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172410"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172410/Modulation_of_Opioid_Transport_at_the_Blood_Brain_Barrier_by_Altered_ATP_Binding_Cassette_ABC_Transporter_Expression_and_Activity"><img alt="Research paper thumbnail of Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity" class="work-thumbnail" src="https://attachments.academia-assets.com/99596295/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172410/Modulation_of_Opioid_Transport_at_the_Blood_Brain_Barrier_by_Altered_ATP_Binding_Cassette_ABC_Transporter_Expression_and_Activity">Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span><span>, Jan 18, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Opioids are highly effective analgesics that have a serious potential for adverse drug reactions ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. Since the use of opioids has escalated in recent years, it is increasingly important to understand biological mechanisms that can increase the probability of opioid-associated adverse events occurring in patient populations. This is emphasized by the current opioid epidemic in the United States where opioid analgesics are frequently abused and misused. It has been established that the effectiveness of opioids is maximized when these drugs readily access opioid receptors in the central nervous system (CNS). Indeed, opioid delivery to the brain is significantly influenced by the blood-brain barrier (BBB). In particular, ATP-binding cassette (ABC) transporters that are endogenously expressed at the BBB are critical determinants of CNS opioid penetration. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172409"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172409/Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels"><img alt="Research paper thumbnail of Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels" class="work-thumbnail" src="https://attachments.academia-assets.com/99596329/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172409/Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels">Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels</a></div><div class="wp-workCard_item"><span>PloS one</span><span>, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The rates of opioid prescription and use have continued to increase over the last few decades res...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The rates of opioid prescription and use have continued to increase over the last few decades resulting in a greater number of opioid tolerant patients. Treatment of acute pain from surgery and injury is a clinical challenge for these patients. Several pain management strategies including prescribing increased opioids are used clinically with limited success; all currently available strategies have significant limitations. Many opioids are a substrate for p-glycoprotein (p-gp), an efflux transporter at the blood-brain barrier (BBB). Increased p-gp is associated with a decreased central nervous system uptake and analgesic efficacy of morphine. Our laboratory previously found that acute peripheral inflammatory pain (PIP) induces p-gp trafficking from the nucleus to the luminal surface of endothelial cells making up the BBB concomitant with increased p-gp activity and decreased morphine analgesic efficacy. In the current study, we tested whether PIP-induced p-gp trafficking could contr...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dd3c125046acdbbc8a4a7a1b5a8cad15" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596329,"asset_id":98172409,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596329/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172409"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172409"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172409; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172409]").text(description); $(".js-view-count[data-work-id=98172409]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172409; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172409']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172409, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "dd3c125046acdbbc8a4a7a1b5a8cad15" } } $('.js-work-strip[data-work-id=98172409]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172409,"title":"Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels","translated_title":"","metadata":{"abstract":"The rates of opioid prescription and use have continued to increase over the last few decades resulting in a greater number of opioid tolerant patients. 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In the current study, we tested whether PIP-induced p-gp trafficking could contr...","internal_url":"https://www.academia.edu/98172409/Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels","translated_internal_url":"","created_at":"2023-03-08T10:38:21.373-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596329,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596329/thumbnails/1.jpg","file_name":"3d1fc087c0ebe4d174b37b94c540e2df5a37.pdf","download_url":"https://www.academia.edu/attachments/99596329/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Chronic_morphine_exposure_potentiates_p.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596329/3d1fc087c0ebe4d174b37b94c540e2df5a37-libre.pdf?1678301627=\u0026response-content-disposition=attachment%3B+filename%3DChronic_morphine_exposure_potentiates_p.pdf\u0026Expires=1732985582\u0026Signature=gjbrfdlzEMe0wnkqHtsZHnfCd6VahJ8OT1~zk7l2dGSh8m-MQPlsbhkd54Cz6s0vIdqgb2yiT7W4ngFxkucUqTZzoL~BIhM~8ln74EPrBjJa00c1yKDze6MYGUcaijKHhOwwse6MLoUnYuUceAZ4o0pM~t6SXem7THKXyTeMdcqnrzrxtEhHPCKtu1P4JoFRucZF29T21Ivj-7opf4DpPgAJdSkNaHwLAHb9gjxqBb9v~j2KVkCprKFFhz0uBLvZXX0-rKxXtXdaUtnj9RRB9CNsYwPt-YpDkkFEL-QvtdnezEuwBLVzVMJSRMOV-ftDwT3b7TdrxHWipIchB4o7Mg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Chronic_morphine_exposure_potentiates_p_glycoprotein_trafficking_from_nuclear_reservoirs_in_cortical_rat_brain_microvessels","translated_slug":"","page_count":16,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596329,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596329/thumbnails/1.jpg","file_name":"3d1fc087c0ebe4d174b37b94c540e2df5a37.pdf","download_url":"https://www.academia.edu/attachments/99596329/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Chronic_morphine_exposure_potentiates_p.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596329/3d1fc087c0ebe4d174b37b94c540e2df5a37-libre.pdf?1678301627=\u0026response-content-disposition=attachment%3B+filename%3DChronic_morphine_exposure_potentiates_p.pdf\u0026Expires=1732985582\u0026Signature=gjbrfdlzEMe0wnkqHtsZHnfCd6VahJ8OT1~zk7l2dGSh8m-MQPlsbhkd54Cz6s0vIdqgb2yiT7W4ngFxkucUqTZzoL~BIhM~8ln74EPrBjJa00c1yKDze6MYGUcaijKHhOwwse6MLoUnYuUceAZ4o0pM~t6SXem7THKXyTeMdcqnrzrxtEhHPCKtu1P4JoFRucZF29T21Ivj-7opf4DpPgAJdSkNaHwLAHb9gjxqBb9v~j2KVkCprKFFhz0uBLvZXX0-rKxXtXdaUtnj9RRB9CNsYwPt-YpDkkFEL-QvtdnezEuwBLVzVMJSRMOV-ftDwT3b7TdrxHWipIchB4o7Mg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience"},{"id":2827,"name":"Mental Health","url":"https://www.academia.edu/Documents/in/Mental_Health"},{"id":2898,"name":"Pain","url":"https://www.academia.edu/Documents/in/Pain"},{"id":17960,"name":"Infectious Diseases","url":"https://www.academia.edu/Documents/in/Infectious_Diseases"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":40165,"name":"Pain Management","url":"https://www.academia.edu/Documents/in/Pain_Management"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain"},{"id":218374,"name":"Morphine","url":"https://www.academia.edu/Documents/in/Morphine"},{"id":220780,"name":"PLoS one","url":"https://www.academia.edu/Documents/in/PLoS_one"},{"id":317801,"name":"Cell nucleus","url":"https://www.academia.edu/Documents/in/Cell_nucleus"},{"id":568887,"name":"Carrageenan","url":"https://www.academia.edu/Documents/in/Carrageenan"},{"id":632073,"name":"CNS","url":"https://www.academia.edu/Documents/in/CNS"},{"id":711582,"name":"Opioid","url":"https://www.academia.edu/Documents/in/Opioid"},{"id":820245,"name":"Analgesic","url":"https://www.academia.edu/Documents/in/Analgesic"},{"id":1310914,"name":"BBB","url":"https://www.academia.edu/Documents/in/BBB"},{"id":1796876,"name":"Microvessels","url":"https://www.academia.edu/Documents/in/Microvessels"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172408"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172408/Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery"><img alt="Research paper thumbnail of Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery" class="work-thumbnail" src="https://attachments.academia-assets.com/99596314/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172408/Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery">Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery</a></div><div class="wp-workCard_item"><span>eNeuro</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expre...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3797c383dd47c818d519ff1c03c63b84" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596314,"asset_id":98172408,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596314/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172408"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172408"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172408; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172408]").text(description); $(".js-view-count[data-work-id=98172408]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172408; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172408']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172408, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3797c383dd47c818d519ff1c03c63b84" } } $('.js-work-strip[data-work-id=98172408]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172408,"title":"Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery","translated_title":"","metadata":{"abstract":"Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expre...","publication_name":"eNeuro"},"translated_abstract":"Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expre...","internal_url":"https://www.academia.edu/98172408/Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery","translated_internal_url":"","created_at":"2023-03-08T10:38:21.254-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":38289730,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":99596314,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596314/thumbnails/1.jpg","file_name":"ENEURO.0116-18.2018.full.pdf","download_url":"https://www.academia.edu/attachments/99596314/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Loss_of_Blood_Brain_Barrier_Integrity_in.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596314/ENEURO.0116-18.2018.full-libre.pdf?1678301424=\u0026response-content-disposition=attachment%3B+filename%3DLoss_of_Blood_Brain_Barrier_Integrity_in.pdf\u0026Expires=1732985582\u0026Signature=XbJczqBMqvNW4mgTYBSXZJ-eWB6G~M-LyQAKbQAE6NfD5jR~SWAtzb8UHsrYS1mU9dLQ1UEeL1YrXojYShx8sVB5ucD93I2E0r-iMp5ZuTaIxPGmzvax2w7COejgQ59LKsFF4lV5xeqYsjFMcobYQ-OJzmEupbG6aTc9ElztzccF~D6lS3ZY9kwCMXWSxuXkz9tO84IaVF6hF4rwKqqJ0~7RiOkyJdyNW0E3hWbre7SCM55y1UbzJLtUyOx4AIl~HICddDuY67NchKG~j6BdxTT9veDGz3V3OVlxPEMOWsIqHL8VnQiYyzVha22ZGxI5BDzthbxef9WIZAHb1Ggz0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Loss_of_Blood_Brain_Barrier_Integrity_in_a_KCl_Induced_Model_of_Episodic_Headache_Enhances_CNS_Drug_Delivery","translated_slug":"","page_count":14,"language":"en","content_type":"Work","owner":{"id":38289730,"first_name":"Thomas","middle_initials":null,"last_name":"Davis","page_name":"ThomasDavis24","domain_name":"independent","created_at":"2015-11-13T16:43:14.395-08:00","display_name":"Thomas Davis","url":"https://independent.academia.edu/ThomasDavis24"},"attachments":[{"id":99596314,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/99596314/thumbnails/1.jpg","file_name":"ENEURO.0116-18.2018.full.pdf","download_url":"https://www.academia.edu/attachments/99596314/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Loss_of_Blood_Brain_Barrier_Integrity_in.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/99596314/ENEURO.0116-18.2018.full-libre.pdf?1678301424=\u0026response-content-disposition=attachment%3B+filename%3DLoss_of_Blood_Brain_Barrier_Integrity_in.pdf\u0026Expires=1732985582\u0026Signature=XbJczqBMqvNW4mgTYBSXZJ-eWB6G~M-LyQAKbQAE6NfD5jR~SWAtzb8UHsrYS1mU9dLQ1UEeL1YrXojYShx8sVB5ucD93I2E0r-iMp5ZuTaIxPGmzvax2w7COejgQ59LKsFF4lV5xeqYsjFMcobYQ-OJzmEupbG6aTc9ElztzccF~D6lS3ZY9kwCMXWSxuXkz9tO84IaVF6hF4rwKqqJ0~7RiOkyJdyNW0E3hWbre7SCM55y1UbzJLtUyOx4AIl~HICddDuY67NchKG~j6BdxTT9veDGz3V3OVlxPEMOWsIqHL8VnQiYyzVha22ZGxI5BDzthbxef9WIZAHb1Ggz0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":98913,"name":"Blood brain barrier","url":"https://www.academia.edu/Documents/in/Blood_brain_barrier"},{"id":763475,"name":"Allodynia","url":"https://www.academia.edu/Documents/in/Allodynia"},{"id":1371582,"name":"Tight Junction","url":"https://www.academia.edu/Documents/in/Tight_Junction"},{"id":1798986,"name":"Cortical Spreading Depression","url":"https://www.academia.edu/Documents/in/Cortical_Spreading_Depression"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="98172407"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/98172407/Functional_Expression_of_P_glycoprotein_and_Organic_Anion_Transporting_Polypeptides_at_the_Blood_Brain_Barrier_Understanding_Transport_Mechanisms_for_Improved_CNS_Drug_Delivery"><img alt="Research paper thumbnail of Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?" class="work-thumbnail" src="https://attachments.academia-assets.com/99596312/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/98172407/Functional_Expression_of_P_glycoprotein_and_Organic_Anion_Transporting_Polypeptides_at_the_Blood_Brain_Barrier_Understanding_Transport_Mechanisms_for_Improved_CNS_Drug_Delivery">Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?</a></div><div class="wp-workCard_item"><span>The AAPS journal</span><span>, Jul 26, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="73b4c43609d71ef3a81b4e25cda638f7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":99596312,"asset_id":98172407,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/99596312/download_file?st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&st=MTczMjk4MTk4Miw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="98172407"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="98172407"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 98172407; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=98172407]").text(description); $(".js-view-count[data-work-id=98172407]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 98172407; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='98172407']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 98172407, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "73b4c43609d71ef3a81b4e25cda638f7" } } $('.js-work-strip[data-work-id=98172407]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":98172407,"title":"Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?","translated_title":"","metadata":{"abstract":"Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. 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With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. 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