Dynamic changes of the gene, protein and neural progenitors in the monkey hippocampus after ischemia

以下是过去三年使用脑损伤-全脑缺血模型的主要发现。1)我们发现，缺血可以增加成年猴海马中NPC的数量，类似于啮齿动物的大脑，但猴子的反应远低于啮齿动物的反应-数量的10倍，更重要的是-产生神经元的能力-15倍（神经元分化）（Mol Cell Neurosci 23:29 -301,2003）。2)此外，猴子NPC不能替代缺血易感的CA1区中的任何神经元（Glia 42;209-224,2003），这表明它们不能在没有外部影响的情况下介导临床显著效果。3)最近，我们发现了啮齿动物NPC与猴子NPC之间差异的潜在分子解释——啮齿动物NPC在CA1区表达促进神经发生的发育转录因子Pax6、Emx2和Ngn2，而猴子NPC在CA1区不表达这些蛋白。4)重要的是，我们已经确定了血管外膜周围的血管生态位，它可以促进猴齿状回的神经发生，但不能促进CA1区（海马14:861-875,2004）。5)最后，我们首次描述了脑缺血后鼻窦炎在侧脑室SVZ和嗅球中的上调，以及脑缺血后猴新皮层和纹状体中有限的神经元生成（J Neurosci Res 81:776-788,2005）。6)因此，申请人的小组研究了灵长类动物端脑的所有主要区域与脑缺血后神经发生的关系。

The followings are main findings of the past three years, using a model of cerebral injury-global ischemia.1)We found that ischemia can increase the number of NPC in adult monkey hippocampus similarly to the rodent brain, but the monkey response was much lower than the rodent response-10 times in quantity, and more importantly-15 times in ability to produce neurons (neuronal differentiation) (Mol Cell Neurosci 23:292-301,2003).2)Further, monkey NPC were unable to replace any neurons in the ischemia-vulnerable CA1 sector (Glia 42;209-224,2003), which suggests that they cannot mediate a clinically-significant effect without an external influence.3)Recently, we have identified potential molecular explanation for this discrepancy between rodent and monkey NPC-while rodent NPC in CA1 sector express the developmental transcription factors Pax6,Emx2 and Ngn2 that can promote neurogenesis, monkey NPC in CA1 did not express these proteins.4)Importantly, we have identified a vascular niche around the adventitia of blood vessels that can promote neurogenesis in monkey dentate gyrus but not in CA1 sector (Hippocampus 14:861-875,2004).5)Lastly, we were the first to describe postischemic NPC upregulation in SVZ of the lateral ventricle, also in the olfactory bulb, and a limited neuronal production in the postischemic monkey neocortex and striatum (J Neurosci Res 81:776-788,2005).6)Thus, the applicant's group has investigated all major regions in the primate telencephalon with respect to postischemic neurogenesis.