VEGF in Neurprotection and Neurogenesis

超出所提供的空间。血管内皮生长因子（VEGF或VEGF-A）是一种可与内皮细胞上的受体酪氨酸激酶相互作用以促进血管生成的低氧诱导分泌蛋白。最近的证据表明，VEGF也可以直接作用于神经元以产生神经营养和神经保护作用，并且作用于成人脑中的神经元前体细胞以刺激神经发生-前体细胞向成熟神经元表型分化的过程。这项工作的广泛的总体目标是了解VEGF如何影响神经元及其细胞前体，并确定VEGF在中风和其他神经系统疾病中可能的治疗作用。该提议的基础假设是VEGF直接作用于（A）脑神经元以保护它们免受缺氧、缺血和相关损伤，和（B）神经元前体以促进神经发生。具体目标是：（1）确定VEGF通过其保护皮质神经元免受体外模拟缺血和相关损伤的受体和信号转导途径，（2）研究VEGF通过其保护神经元免受体内局灶性脑缺血的机制，（3）确定VEGF通过其刺激体外大脑皮质培养物中的神经发生的机制，和（4）表征VEGF在体内的神经发生促进作用，涉及哪些神经增殖区受影响，哪些VEGF受体参与，无论该作用是通过刺激细胞分裂还是抑制细胞死亡产生，以及靶细胞的迁移和功能命运。性能现场=

EXCEED THE SPACE PROVIDED. Vascular endothelial growth factor (VEGF or VEGF-A) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. Recent evidence indicates that VEGF may also act directly on neurons to produce neurotrophic and neuroprotective effects, and on neuronal precursor cells in the adult brain to stimulate neurogenesis -- the process through which precursor cells differentiate towards a mature neuronal phenotype. The broad, overall objective of this work is to understand how VEGF affects neurons and their cellular precursors, and to identify possible therapeutic roles for VEGF in stroke and other neurological disorders. The hypothesis underlying this proposal is that VEGF acts directly on (A) cerebral neurons to protect them from hypoxia, ischemia and related insults and (B) neuronal precursors to promote neurogenesis. The specific aims are to: (1) define the receptors and signal-transduction pathways through which VEGF protects cortical neurons from simulated ischemia and related insults in vitro, (2) investigate the mechanism by which VEGF protects neurons from focal cerebral ischemia in vivo, (3) determine the mechanism by which VEGF stimulates neurogenesis in cerebral cortical cultures in vitro, and (4) characterize the neurogenesis-promoting effect of VEGF in vivo with respect to which neuroproliferative zones are affected, which VEGF receptors are involved, whether the effect is produced by stimulating cell division or inhibiting cell death, and the migratory and functional fates of the target cells. PERFORMANCE SITE ========================================Section End===========================================