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This phenomenon is largely mediated by endothelial-produced brain-derived neurotrophic factor (BDNF) because filtering endothelial-conditioned media with TrkB-Fc eliminates the neuroprotective effect. Endothelial production of BDNF is sustained by \u03b2-1 integrin and integrin-linked kinase (ILK) signaling. Noncytotoxic levels of oxidative stress disrupts ILK signaling and reduces endothelial levels of neuroprotective BDNF. These data suggest that cerebral endothelium provides a critical source of homeostatic support for neurons. Targeting these signals of matrix and trophic coupling between endothelium and neurons may provide new therapeutic opportunities for stroke and other CNS disorders.<\/jats:p>","DOI":"10.1073\/pnas.0801105105","type":"journal-article","created":{"date-parts":[[2008,5,21]],"date-time":"2008-05-21T21:30:13Z","timestamp":1211405413000},"page":"7582-7587","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":230,"title":["Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons"],"prefix":"10.1073","volume":"105","author":[{"given":"Shuzhen","family":"Guo","sequence":"first","affiliation":[{"name":"*Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jean","family":"Kim","sequence":"additional","affiliation":[{"name":"*Neuroprotection 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