Ischemic preconditioning in the brain
Ischemic preconditioning in the brain
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DOI：
10.1097/00001503-200310000-00002
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发表时间：
2003-10-01
影响因子：
2.5
通讯作者：
Patel, Piyush M.
中科院分区：
文献类型：
--
作者：
Davis, Daniel P.;Patel, Piyush M.
综述目的脑缺血是心血管手术相关的重要发病率和死亡率的原因，是多种疾病状态的最终结果，包括心脏骤停、中风和创伤性脑损伤。尽管有大量资源致力于开发神经保护策略，但在这方面取得的进展甚微。神经元缺血预处理是一种内源性神经保护策略，可提供持续和强大的缺血耐受。鉴定负责介导预处理反应的机制可能提供新的治疗靶点，并进一步加深我们对脑损伤的自然适应的理解。最近的研究结果最近的研究工作已经阐明了许多细胞内信号通路，最终导致缺血耐受后的预处理刺激。其中大多数与谷氨酸受体信号转导、细胞内激酶和几种转录调节因子有关。微阵列分析已经确定了几个基因家族，值得进一步研究，以确定新的候选人的神经保护疗法。这些基因包括参与突触结构和信号传播，细胞周期和转录调节因子，和介导的细胞凋亡，如热休克蛋白和抗凋亡的线粒体proteines.SummaryNeuronal缺血预处理是一种内源性机制，导致强大的神经保护缺血。启动预处理和候选基因介导这种现象的上游途径的鉴定可能提供新的治疗靶点，适用于各种疾病状态和围手术期并发症。
Purpose of reviewBrain ischemia is responsible for significant morbidity and mortality associated with cardiovascular surgery, and is the end result of multiple disease states, including cardiac arrest, stroke, and traumatic brain injury. Despite significant resources dedicated to developing neuroprotective strategies, little progress has been made in this regard. Neuronal ischemic preconditioning is an endogenous neuroprotective strategy that provides sustained and robust ischemic tolerance. Identification of the mechanisms responsible for mediating the preconditioning response may offer novel therapeutic targets and further our understanding of the natural adaptations to brain injury.Recent findingsRecent research efforts have elucidated many intracellular signaling pathways that ultimately lead to ischemic tolerance after a preconditioning stimulus. Most of these are associated with glutamate receptor signal transduction, the intracellular kinases, and several transcription regulators. Microarray analysis has identified several gene families that warrant further investigation to identify novel candidates for neuroprotective therapies. These include genes involved in synaptic architecture and signal propagation, cell cycle and transcription regulators, and mediators of apoptosis such as the heat shock proteins and anti-apoptotic mitochondrial proteins.SummaryNeuronal ischemic preconditioning is an endogenous mechanism that leads to robust neuroprotection from ischemia. Identification of the upstream pathways that initiate preconditioning and candidate genes that mediate this phenomenon may offer novel therapeutic targets, with applicability to a variety of disease states and perioperative complications.