Generation of new neurons persists in the normal adult mammalian brain, with neural stem/progenitor cells residing in at least two brain regions: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG). Adult neurogenesis is well documented in the rodent, and has also been demonstrated in vivo in nonhuman primates and humans. Brain injuries such as ischemia affect neurogenesis in adult rodents as both global and focal ischemic insults enhance the proliferation of progenitor cells residing in SGZ or SVZ. We addressed the issue whether an injury triggered activation of endogenous neuronal precursors also takes place in the adult primate brain. We found that the ischemic insult increased the number of progenitor cells in monkey SGZ and SVZ, and caused gliogenesis in the ischemia-prone hippocampal CA1 sector. To better understand the mechanisms regulating precursor cell division and differentiation in the primate, we analyzed the expression at protein level of a panel of potential regulatory molecules, including neurotrophic factors and their receptors. We found that a fraction of mitotic progenitors were positive for the neurotrophin receptor TrkB, while immature neurons expressed the neurotrophin receptor TrkA. Astroglia, ependymal cells and blood vessels in SVZ were positive for distinctive sets of ligands/receptors, which we characterized. Thus, a network of neurotrophic signals operating in an autocrine or paracrine manner may regulate neurogenesis in adult primate SVZ. We also analyzed microglial and astroglial proliferation in postischemic hippocampal CA1 sector. We found that proliferating postischemic microglia in adult monkey CA1 sector express the neurotrophin receptor TrkA, while activated astrocytes were labeled for nerve growth factor (NGF), ligand for TrkA, and the tyrosine kinase TrkB, a receptor for brain derived neurotrophic factor (BDNF). These results implicate NGF and BDNF as regulators of postischemic glial proliferation in adult primate hippocampus.

中文翻译：

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灵长类动物的脑缺血，神经发生和神经营养受体表达。

新的神经元的生成持续存在于正常的成年哺乳动物脑中，神经干/祖细胞至少存在于两个大脑区域：侧脑室的脑室下区域（SVZ）和齿状回（DG）的颗粒下区域（SGZ） 。成年神经发生在啮齿动物中有充分记载，并且还已经在非人类灵长类动物和人类体内得到证实。诸如缺血之类的脑损伤会影响成年啮齿动物的神经发生，因为整体性和局部缺血性损伤均会促进SGZ或SVZ中祖细胞的增殖。我们解决了在成人灵长类动物大脑中是否也发生过损伤触发内源性神经元前体激活的问题。我们发现缺血性损伤增加了猴子SGZ和SVZ中祖细胞的数量，并在易缺血的海马CA1区引起胶质生成。为了更好地了解在灵长类中调节前体细胞分裂和分化的机制，我们分析了一组潜在调节分子（包括神经营养因子及其受体）在蛋白质水平上的表达。我们发现一部分有丝分裂祖细胞对神经营养蛋白受体TrkB呈阳性，而未成熟的神经元则表达神经营养蛋白受体TrkA。SVZ中的星形胶质细胞，室管膜细胞和血管对我们所表征的独特的配体/受体集呈阳性。因此，以自分泌或旁分泌方式运行的神经营养信号网络可调节成年灵长类动物SVZ中的神经发生。我们还分析了缺血后海马CA1区的小胶质细胞和星形胶质细胞增殖。我们发现成年猴CA1区的局部缺血后小胶质细胞表达神经营养蛋白受体TrkA，而活化的星形胶质细胞被标记为神经生长因子（NGF），TrkA的配体和酪氨酸激酶TrkB（脑源性神经营养因子（BDNF）的受体） 。这些结果暗示了NGF和BDNF是成年灵长类海马中缺血后神经胶质增生的调节剂。