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Proc Natl Acad Sci U S A. 2008 May 27;105(21):7582-7. doi: 10.1073/pnas.0801105105. Epub 2008 May 21.

Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons.

Author information

  • 1Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129.

Abstract

The neurovascular unit is an emerging concept that emphasizes homeostatic interactions between endothelium and cerebral parenchyma. Here, we show that cerebral endothelium are not just inert tubes for delivering blood, but they also secrete trophic factors that can be directly neuroprotective. Conditioned media from cerebral endothelial cells broadly protects neurons against oxygen-glucose deprivation, oxidative damage, endoplasmic reticulum stress, hypoxia, and amyloid neurotoxicity. 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 beta-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.

PMID:
18495934
[PubMed - indexed for MEDLINE]
PMCID:
PMC2396701
Free PMC Article

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