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首页> 外文期刊>Translational Stroke Research >Excitatory and Mitogenic Signaling in Cell Death, Blood–brain Barrier Breakdown, and BBB Repair after Intracerebral Hemorrhage
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Excitatory and Mitogenic Signaling in Cell Death, Blood–brain Barrier Breakdown, and BBB Repair after Intracerebral Hemorrhage

机译:脑出血后细胞死亡,血脑屏障破坏和BBB修复的兴奋性和有丝分裂信号

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摘要

Intracerebral hemorrhage (ICH) results in the release of a large number of endogenous molecules, including glutamate, Ca2+, ROS, thrombin, heme, iron, TNF-α, and others. These molecules participate in excitatory and mitogenic signaling transduction in which N-methyl-d-aspartate (NMDA) receptors and Src family kinases (SFKs) are implicated. Mitogenic signaling initiates the cell cycle for normal cell division of microglia and neural progenitor cells, whereas aberrant mitogenic signaling causes toxicity, killing neurons, astrocytes, and brain microvascular endothelial cells in neurological diseases including ICH. In this review, we summarize (1) how SFKs modulate NMDA receptors to kill neurons following ICH and (2) how SFKs modulate mitogenic signaling transduction to kill neurons and play a role in disrupting the blood–brain barrier (BBB) immediately following ICH and in repairing the BBB during the recovery phases weeks following ICH.
机译:脑出血(ICH)导致释放大量内源性分子,包括谷氨酸,Ca2 +,ROS,凝血酶,血红素,铁,TNF-α等。这些分子参与兴奋性和有丝分裂信号转导,其中涉及N-甲基-d-天冬氨酸(NMDA)受体和Src家族激酶(SFK)。有丝分裂信号传导启动小胶质细胞和神经祖细胞正常细胞分裂的细胞周期,而有丝分裂信号传导异常会导致毒性,杀死包括ICH在内的神经系统疾病的神经元,星形胶质细胞和脑微血管内皮细胞。在这篇综述中,我们总结(1)SFK如何调节NMDA受体以杀死ICH后的神经元,(2)SFK如何调节有丝分裂信号转导以杀死神经元并在ICH后立即破坏血脑屏障(BBB)中发挥作用在ICH后数周的恢复阶段修复BBB。

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