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Genetics of Cerebral Vasospasm

机译:脑血管痉挛的遗传学

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Cerebral vasospasm (CV) is a major source of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). It is thought that an inflammatory cascade initiated by extravasated blood products precipitates CV, disrupting vascular smooth muscle cell function of major cerebral arteries, leading to vasoconstriction. Mechanisms of CV and modes of therapy are an active area of research. Understanding the genetic basis of CV holds promise for the recognition and treatment for this devastating neurovascular event. In our review, we summarize the most recent research involving key areas within the genetics and vasospasm discussion: (1)Prognostic role of genetics—risk stratification based on gene sequencing, biomarkers, and polymorphisms; (2)Signaling pathways—pinpointing key inflammatory molecules responsible for downstream cellular signaling and altering these mediators to provide therapeutic benefit; and (3)Gene therapy and gene delivery—using viral vectors or novel protein delivery methods to overexpress protective genes in the vasospasm cascade.
机译:脑血管痉挛(CV)是动脉瘤性蛛网膜下腔出血(aSAH)发病率和死亡率的主要来源。认为由渗出的血液产物引发的炎症级联沉淀了CV,破坏了主要脑动脉的血管平滑肌细胞功能,导致血管收缩。简历的机制和治疗模式是一个活跃的研究领域。了解CV的遗传基础,有望为这一毁灭性的神经血管事件的识别和治疗带来希望。在我们的综述中,我们总结了涉及遗传学和血管痉挛讨论的关键领域的最新研究:(1)遗传学的预后作用-基于基因测序,生物标记和多态性的风险分层; (2)信号通路-查明负责下游细胞信号传导的关键炎症分子,并改变这些介体以提供治疗益处; (3)基因治疗和基因递送-使用病毒载体或新型蛋白质递送方法在血管痉挛级联中过表达保护性基因。

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