当前位置:首页 > 生物研究 > 神经生物学 > 正文

首次探明大脑特定区域抵御中风伤害的机制

首次探明大脑特定区域抵御中风伤害的机制

中风是一种脑血管疾病,由血管阻塞或血管破裂引起,可能导致瘫痪等多种严重后遗症,如果治疗不及时,还可能导致患者死亡。

英国牛津大学等机构的一项最新研究发现,大脑中的海马区在发生中风时会启动“自我保护”机制,分泌一种蛋白质来保护脑细胞,避免因缺氧等造成的伤害。这一发现有助于开发治疗中风等疾病的新药物。相关研究发表在新一期出版的《自然—医学》杂志上。

研究人员表示,中风发生时,血管中形成血栓,可能会导致脑细胞因为氧和葡萄糖等供应不足而死亡。但动物实验显示,大脑中的海马区在中风发生后会迅速分泌一种被称为“错构素”(Hamartin)的蛋白质,它能使这一区域的脑细胞在缺氧缺糖的情况下存活。

这是首次探明大脑特定区域抵御中风伤害的生物学机制,对开发治疗中风及其他神经退化疾病的新方法大有益处。研究人员下一步将探索以小分子药物作为“错构素”替代物的可行性。

了解更多:

Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy

Nature Medicine, 24 February 2013 | doi:10.1038/nm.3097

Previous attempts to identify neuroprotective targets by studying the ischemic cascade and devising ways to suppress it have failed to translate to efficacious therapies for acute ischemic stroke. We hypothesized that studying the molecular determinants of endogenous neuroprotection in two well-established paradigms, the resistance of CA3 hippocampal neurons to global ischemia and the tolerance conferred by ischemic preconditioning (IPC), would reveal new neuroprotective targets. We found that the product of the tuberous sclerosis complex 1 gene (TSC1), hamartin, is selectively induced by ischemia in hippocampal CA3 neurons. In CA1 neurons, hamartin was unaffected by ischemia but was upregulated by IPC preceding ischemia, which protects the otherwise vulnerable CA1 cells. Suppression of hamartin expression with TSC1 shRNA viral vectors both in vitro and in vivo increased the vulnerability of neurons to cell death following oxygen glucose deprivation (OGD) and ischemia. In vivo, suppression of TSC1 expression increased locomotor activity and decreased habituation in a hippocampal-dependent task. Overexpression of hamartin increased resistance to OGD by inducing productive autophagy through an mTORC1-dependent mechanism.

阅读次数:  
更多 相关资讯:
    无相关信息

发表评论