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Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor
Author(s) -
Sun FengYan,
Guo Xin
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20321
Subject(s) - neuroprotection , neurogenesis , pi3k/akt/mtor pathway , subventricular zone , vascular endothelial growth factor , protein kinase b , neuroscience , microbiology and biotechnology , biology , signal transduction , pharmacology , neural stem cell , cancer research , stem cell , vegf receptors
Abstract The present view of the neuroprotective functions and mechanisms of action of vascular endothelial growth factor (VEGF) is based on studies of neuronal ischemic/hypoxic models in vivo and in vitro. Endogenous neuronal VEGF increases in the ischemic brain and plays a neuroprotective role in the pathophysiologic processes that follow stroke. Exogenous VEGF, directly administered or overexpressed by gene delivery into rat brains, reduces ischemic brain infarct and decreases hypoxic neuronal death. The main neuroprotective mechanisms of VEGF include: (1) modulation of the phosphatidylinositol 3′‐kinase (PI3K)/Akt/nuclear factor‐κB signaling pathway, inhibition of caspase‐3 activity, and reduction of ischemic neuronal apoptosis; (2) inhibition of outward delayed rectifier potassium channel currents and increase of ischemia‐induced tyrosine phosphorylation of Kv1.2 potassium channel proteins via activation of the PI3K pathway; and (3) enhancement of proliferation and migration of neural progenitors in the subventricular zone and improvement of striatal neurogenesis and maturation of newborn neurons in adult rat brains after stroke. © 2004 Wiley‐Liss, Inc.