Department of Neurological Surgery, Columbia University, 630 West 168th Street, Room no. 5-454, New York, NY 10032, USA.
J Cereb Blood Flow Metab. 2010 Apr;30(4):676-88. doi: 10.1038/jcbfm.2009.278. Epub 2010 Jan 13.
Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future.
尽管人们已经付出了大量努力来阐明蛛网膜下腔出血（aSAH）后迟发性脑损伤的细胞和分子基础，但这些事件的病理生理学仍知之甚少。最近，许多工作都集中在评估各种疾病的遗传基础上，以确定特定分子途径的贡献，并揭示新的机制。大多数蛛网膜下腔出血的遗传研究都集中在与颅内动脉瘤的发展及其随后的破裂相关的这些标志物的基因表达和连锁研究上。而关于脑血管痉挛、迟发性脑损伤易感性以及 aSAH 后功能结局的遗传决定因素的研究则少得多。可疑基因多种多样，涵盖了多个功能系统，包括纤维蛋白溶解、炎症、血管反应性和神经元修复。为此，我们对 21 项研究进行了系统综述，这些研究表明 aSAH 后的临床结果存在遗传基础，特别强调了脑血管痉挛和迟发性脑缺血的发病机制。此外，我们还强调了遗传关联研究解释中的潜在陷阱，并呼吁未来进行更大规模多中心研究时设计的统一性。
