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

以下是近三年来利用脑损伤-全脑缺血模型的主要研究结果1)我们发现，脑缺血可以增加成年猴海马区NPC的数量，与啮齿类动物的大脑相似，但猴子的反应远低于啮齿类动物的反应-数量是啮齿动物的10倍，更重要的是-15倍的神经元分化(Mol Cell Neurosci 23：292-301,2003)2)此外，猴子的NPC无法取代缺血易受影响的CA1区的任何神经元(Glia 42；3)最近，我们发现了啮齿动物和猴鼻咽癌之间这种差异的潜在分子解释--啮齿类鼻咽癌在CA1区表达促进神经发生的发育转录因子Pax6、Emx2和Ngn2，而猴CA1区鼻咽癌不表达这些蛋白。4)重要的是，我们发现了血管外膜周围的血管生态位可以促进猴齿状回的神经发生，而不是在CA1区(海马14：861-875,2004)。5)最后，我们首次描述了缺血后鼻咽癌在侧脑室SVZ的表达6)因此，申请人的研究小组研究了灵长类动物端脑中关于缺血后神经发生的所有主要区域。

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.