Modeling the neurovascular niche: implications for recovery from CNS injury.
Modeling the neurovascular niche: implications for recovery from CNS injury.
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发表时间：
2009-10
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通讯作者：
Joseph A. Madri
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作者：
Joseph A. Madri
虽然中风、创伤性脑和脊髓损伤、神经退行性疾病和缺氧的生存率在过去几年有所提高，但治疗方法有限，这些损伤和疾病对患者、家庭和社会的影响可能是毁灭性的。从这些损伤中恢复是可变的，并且部分涉及CNS的神经源性区（神经血管龛）中的协调的血管生成和神经发生。在这个集中审查的作用，HIF-1 α介导的反应缺氧中枢神经系统神经血管龛进行了讨论。使用体内和体外亚致死性缺氧小鼠模型，我们模拟了在人群中观察到的可变反应，并将基线和缺氧诱导的HIF-1 α和几种下游信号传导组分（包括BDNF、VEGF、SDF-1、TrkB、Nrp-1、CXCR 4和NO）诱导的差异与存活率以及内皮细胞和神经干细胞存活和增殖的差异相关联，提供了对这一重要和及时的问题的深入了解，并表明优化这些信号传导组分中的一些或全部的表达水平可能具有使CNS损伤后的恢复最大化的潜力。
While survival from stroke, traumatic brain and spinal cord injuries, neurodegenerative diseases and hypoxia has improved over the past several years, treatments are limited and impacts of these injuries and diseases to patients, families and society can be devastating. Recovery from these injuries is variable and involves in part an orchestrated angiogenesis and neurogenesis in the neurogenic zones (neurovascular niches) of the CNS. In this focused review the roles of HIF-1alpha mediated responses to hypoxia in CNS neurovascular niches is discussed. Using in vivo and in vitro murine models of sublethal hypoxia we mimicked the variable responses observed in the human population and correlated differences in baseline and hypoxia-induced induction of HIF-1alpha and several downstream signaling components including BDNF, VEGF, SDF-1, TrkB, Nrp-1, CXCR4 and NO with differences in survival as well as endothelial cell and neural stem cell survival and proliferation, providing insight into this important and timely problem and suggesting that optimization of expression levels of some or all of these signaling components may have the potential of maximizing recovery following CNS injury.