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A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement. edema | electron microscopy | homeostasis | membrane | swelling M ore than 100 y have elapsed since it was first shown that some solutes present in blood are retained by brain capillaries, pointing to the existence of a barrier function at the bloodbrain interface. This early finding naturally inspired a discussion as to what could constitute the morphological substrate of this barrier (1). With the advent of the electron microscope it became clear that the blood-brain interface is composed of endothelia and pericytes, surrounded by a basal lamina and perivascular endfeet of astrocytes. After decades of intense debate, a concept emerged that the functional barrier resides at the level of the endothelial cells (2). This was consistent with morphological data, which clearly showed that endothelia were continuous and coupled by tight junctions (3). The perivascular endfeet, on the other hand, were not coupled by tight junctions and were portrayed as a discontinuous layer with spacious clefts separating the individual processes.","publication_date":"2011,,","publication_name":"Proceedings of the National Academy of Sciences","grobid_abstract_attachment_id":"44015562"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [45800985,45640687,45676113,45608458,306265]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = 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