Protecting neurons
Protecting neurons
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DOI：
10.1111/j.1528-1167.2005.00302.x
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发表时间：
2005-01-01
期刊：
影响因子：
5.6
通讯作者：
Ferriero, DM
中科院分区：
文献类型：
--
作者：
Ferriero, DM
脑损伤会随着时间的推移而发展，通常需要几天甚至几周的时间才能完全发展。这是一个动态过程，涉及直接氧化应激和兴奋性毒性，随后是炎症和预编程细胞死亡。本文简要介绍了发育中的大脑神经保护机制。虽然重点是缺血性损伤，得出的结论适用于任何类型的脑损伤癫痫发作，创伤，或ischemia.Strategies的神经保护包括抢救神经元通过使用有针对性的药物治疗，保护神经元通过预处理，和修复神经元通过增强神经发生。抑制即时和下游损伤后事件影响的药物治疗在保护脑免受缺血性损伤方面仅适度有效。在实验模型中，完全或真正的保护只能通过预处理来实现，预处理是一个动物对致命压力源产生耐受性的过程。虽然没有临床用途，预处理模型提供了宝贵的洞察力如何修复系统在大脑中工作。累积的证据表明，在预处理过程中上调的相同基因，即那些介导真正保护的基因，在损伤和修复过程中也上调。具体而言，低氧预处理和缺氧缺血性损伤已被证明诱导缺氧诱导因子-1（HIF-1）及其靶向存活基因，血管内皮生长因子（VEGF）和促红细胞生成素（Epo）在啮齿动物中。特别令人感兴趣的是Epo的上调，Epo是一种在治疗缺血性中风中可能具有治疗潜力的生长因子。然而，此时，损伤后神经发生的增强似乎为脑损伤后持久的功能恢复提供了最好的希望。
Brain injury evolves overtime, often taking days or even weeks to fully develop. It is a dynamic process that involves immediate oxidative stress and excitotoxicity followed by inflammation and preprogrammed cell death. This article presents a brief overview of mechanisms of neuroprotection in the developing brain. Although the focus is on ischemic injury, the conclusions drawn apply to any type of brain insult-epileptic seizures, trauma, or ischemia.Strategies of neuroprotection include salvaging neurons through the use of targeted pharmacotherapies, protecting neurons through preconditioning, and repairing neurons by enhancing neurogenesis. Drug therapies that dampen the impact of immediate and downstream postinjury events are only modestly effective in protecting the brain from ischemic injury. In experimental models, complete or true protection can be achieved only through preconditioning, a process during which an animal develops tolerance to an otherwise lethal stressor. Although of no clinical use, preconditioning models have provided valuable insight into how repair systems work in the brain. Cumulative evidence indicates that the same genes that are upregulated during preconditioning, those mediating true protection, are also upregulated during injury and repair. Specifically, hypoxic preconditioning and hypoxic-ischemic insult have been shown to induce hypoxia inducible factor-1 (HIF-1) and its target survival genes, vascular endothelial growth factor (VEGF), and erythropoietin (Epo) in rodents. Of particular interest is the upregulation of Epo, a growth factor that may have therapeutic potential in the treatment of ischemic stroke. At this time, however, the postinjury enhancement of neurogenesis appears to offer the best hope for long-lasting functional recovery following brain injury.