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

Shuzhen Guo, Woo Jean Kim, Josephine Lok, Sun Ryung Lee, Elaine Besancon, Bing Hao Luo, Monique F. Stins, Xiaoying Wang, Shoukat Dedhar, Eng H. Lo

Research output: Contribution to journalArticle

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 β-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.

Original languageEnglish (US)
Pages (from-to)7582-7587
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number21
DOIs
StatePublished - May 27 2008

    Fingerprint

Keywords

  • Brain injury
  • Neurodegeneration
  • Neurovascular
  • Stroke

ASJC Scopus subject areas

  • General

Cite this