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Logo of neuroscibullNeuroscience Bulletin
 
Neurosci Bull. 2009 June; 25(3): 139–152.
Published online 2009 July 7. doi:  10.1007/s12264-009-0104-3
PMCID: PMC5552559

Language: English | Chinese

The mechanisms of brain ischemic insult and potential protective interventions

脑缺血的损伤机制及其保护性干预

Abstract

The mechanisms of brain ischemic insult include glutamate excitoxicity, calcium toxicity, free radicals, nitric oxide, inflammatory reactions, as well as dysfunctions of endoplasmic reticulum and mitochondrion. These injury cascades are interconnected in complex ways, thus it is hard to compare their pathogenic importances in ischemia models. And the research in cellular and molecular pathways has spurred the studies in potential neuroprotections mainly in pharmacological fields, such as anti-excitotoxic treatment, calcium-channel antagonism, approaches for inhibition of oxidation, inflammation and apoptosis, etc. Besides, other protective interventions including thrombolysis, arteriogenesis, regeneration therapy, and ischemia preconditioning or postconditioning, are also under investigations. Despite the present difficulties, we are quite optimistic towards future clinical applications of neuroprotective agents, by optimizing experimental approaches and clinical trials.

Key words: brain ischemia, glutamate receptors, calcium toxicity, endoplasmic reticulum stress, neuroprotection

摘要

脑缺血的损伤机制包括谷氨酸兴奋毒性、 钙毒性、 自由基、 一氧化氮、 炎性反应以及内质网和线粒体功能障碍等。 这些损伤性级联反应相互联系, 错综复杂, 很难比较它们在不同模型中的主次作用。 越来越多的对细胞及分子损伤途径的基础研究, 推动了对脑保护治疗的研究。 迄今为止, 脑保护治疗仍以药物治疗为主, 例如, 抗兴奋毒性治疗、 钙通道阻滞、 抗氧化、 抗炎、 抗凋亡治疗等。 此外一些研究还包括溶栓、 动脉生成和神经元再生, 以及缺血前适应和缺血后适应等。 虽然将这些研究成果应用于临床还存在许多困难, 但是通过改进动物实验和临床实验方法, 我们有理由对脑保护治疗持乐观的态度。

关键词: 脑缺血, 谷氨酸受体, 钙毒性, 内质网应激, 脑保护

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