VEGF in Neurprotection and Neurogenesis

血管内皮生长因子(血管内皮生长因子或血管内皮生长因子-A)是一种低氧诱导的相互作用的分泌性蛋白 与内皮细胞上的受体酪氨酸激酶一起促进血管生成。最近的证据表明 血管内皮生长因子也可能直接作用于神经元，产生神经营养和神经保护作用，并在 成人大脑中刺激神经发生的神经前体细胞--通过这个过程 前体细胞分化为成熟的神经元表型。这项工作的总体目标是广泛的 是为了了解血管内皮生长因子如何影响神经元及其细胞前体，并确定可能的 血管内皮生长因子在中风和其他神经疾病中的治疗作用。这背后的假设是 建议是，血管内皮生长因子直接作用于(A)脑神经元，以保护它们免受缺氧、缺血和 相关的侮辱和(B)促进神经发生的神经元前体。具体目标是：(1)界定 血管内皮生长因子保护大脑皮层神经元的受体和信号转导途径 体外模拟缺血及相关损伤，(2)探讨血管内皮细胞生长因子的保护机制 在体局灶性脑缺血神经元，(3)确定VEGF刺激的机制 大脑皮层体外培养中的神经发生，以及(4)表征丹参促进神经发生的作用。 体内哪些神经增殖区受影响，哪些受体是 无论是通过刺激细胞分裂还是抑制细胞死亡而产生的效应，以及迁移 以及靶细胞的功能命运。

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.