Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor.
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-kappaB 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.
Sun
Feng-Yan
FY
National Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, 138 Xue-Yuan Road, Shanghai 200 032, P.R. China. fysun@shmu.edu.cn
Guo
Xin
X
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051663:Kv1.2 Potassium Channel; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
C496969:KCNA2 protein, human; D051663:Kv1.2 Potassium Channel; D018696:Neuroprotective Agents; D024642:Potassium Channels, Voltage-Gated; D042461:Vascular Endothelial Growth Factor A