Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Neurobiol Dis. 2010 Feb;37(2):267-74. doi: 10.1016/j.nbd.2009.11.002. Epub 2009 Nov 10.
Neural stem cells persist in the adult mammalian forebrain and are a potential source of neurons for repair after brain injury. The two main areas of persistent neurogenesis, the subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus, are stimulated by brain insults such as stroke or trauma. Here we focus on the effects of focal cerebral ischemia on SVZ neural progenitor cells in experimental stroke, and the influence of mechanical injury on adult hippocampal neurogenesis in models of traumatic brain injury (TBI). Stroke potently stimulates forebrain SVZ cell proliferation and neurogenesis. SVZ neuroblasts are induced to migrate to the injured striatum, and to a lesser extent to the peri-infarct cortex. Controversy exists as to the types of neurons that are generated in the injured striatum, and whether adult-born neurons contribute to functional restoration remains uncertain. Advances in understanding the regulation of SVZ neurogenesis in general, and stroke-induced neurogenesis in particular, may lead to improved integration and survival of adult-born neurons at sites of injury. Dentate gyrus cell proliferation and neurogenesis similarly increase after experimental TBI. However, pre-existing neuroblasts in the dentate gyrus are vulnerable to traumatic insults, which appear to stimulate neural stem cells in the SGZ to proliferate and replace them, leading to increased numbers of new granule cells. Interventions that stimulate hippocampal neurogenesis appear to improve cognitive recovery after experimental TBI. Transgenic methods to conditionally label or ablate neural stem cells are beginning to further address critical questions regarding underlying mechanisms and functional significance of neurogenesis after stroke or TBI. Future therapies should be aimed at directing appropriate neuronal replacement after ischemic or traumatic injury while suppressing aberrant integration that may contribute to co-morbidities such as epilepsy or cognitive impairment.
神经干细胞存在于成年哺乳动物的前脑中，是脑损伤后修复神经元的潜在来源。两个主要的持续神经发生区域，侧脑室下区（SVZ）-嗅球途径和海马齿状回，受到脑损伤如中风或创伤的刺激。在这里，我们重点关注局灶性脑缺血对实验性中风中 SVZ 神经祖细胞的影响，以及机械损伤对创伤性脑损伤（TBI）模型中成年海马神经发生的影响。中风强烈刺激前脑 SVZ 细胞增殖和神经发生。SVZ 神经前体细胞被诱导迁移到损伤的纹状体，在较小程度上迁移到梗死周围皮质。关于在损伤的纹状体中产生的神经元类型存在争议，并且成年出生的神经元是否有助于功能恢复仍然不确定。对 SVZ 神经发生的调节的理解的进展，特别是中风诱导的神经发生，可能导致受伤部位成年出生的神经元更好地整合和存活。实验性 TBI 后，齿状回细胞增殖和神经发生也同样增加。然而，齿状回中的预先存在的神经前体细胞容易受到创伤性刺激，这似乎刺激 SGZ 中的神经干细胞增殖并取代它们，导致新颗粒细胞数量增加。刺激海马神经发生的干预措施似乎可以改善实验性 TBI 后的认知恢复。条件性标记或消融神经干细胞的转基因方法开始进一步解决中风或 TBI 后神经发生的潜在机制和功能意义的关键问题。未来的治疗方法应该旨在指导缺血性或创伤性损伤后的适当神经元替代，同时抑制可能导致癫痫或认知障碍等合并症的异常整合。
