Pathophysiology, treatment, and animal and cellular models of human ischemic stroke.
Pathophysiology, treatment, and animal and cellular models of human ischemic stroke.
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DOI：
10.1186/1750-1326-6-11
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发表时间：
2011-01-25
影响因子：
15.1
通讯作者：
Arumugam TV
中科院分区：
文献类型：
--
作者：
Woodruff TM;Thundyil J;Tang SC;Sobey CG;Taylor SM;Arumugam TV
中风是世界上第二大死亡原因，存活患者的严重发病率很高。目前有相对较少的治疗选择，以尽量减少中风后的组织死亡。因此，迫切需要在分子、细胞、组织和全身水平上探索导致缺血性脑事件后CNS组织损伤和死亡的机制。本文综述了缺血性脑卒中的病因和发病机制，并提供了缺血性脑卒中的一般模型。脑缺血性损伤的病理生理学解释，和实验动物模型的全球和局灶性缺血性中风，并在体外细胞中风模型，详细描述了沿着实验策略，以分析损伤。特别是，这些中风模型的技术方面进行了评估和批判性评价，沿着详细描述了目前最佳实践的缺血性中风小鼠模型。最后，我们回顾了在实验模型中使用不同策略的临床前研究，然后对最近在人体临床试验中神经保护的失败尝试的结果进行了评估。我们还探索预防和治疗中风的新方法和新兴方法。在这方面，我们注意到，迄今为止，用于中风治疗的单靶点药物疗法在临床试验中普遍失败。需要研究新的中风治疗的目标，这在大脑中具有多效性的治疗效果，探索作为一种替代策略，并阐述了一些这样的可能的目标。开发缺血性卒中的治疗方法本质上是一项困难的工作。病因的多样性、大脑解剖结构的复杂性以及受害者接受及时有效治疗的实际性，都不利于开发有效的药物疗法。这绝不应该成为研究的障碍，相反，这是一个号角，要求加紧努力，减轻这一共同健康灾难造成的痛苦和死亡。本文旨在总结目前的实验和临床最新技术，并指导未来的研究方向。
Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions.
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影响因子：
8.3
作者：
Alvarez-Sabin, Jose;Huertas, Rafael;Montaner, Joan
通讯作者：
Montaner, Joan
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
DOI：
10.1016/s1385-299x(00)00024-6
发表时间：
2000-07-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
--
作者：
Bledi, Y;Domb, AJ;Linial, M
通讯作者：
Linial, M
DOI：
10.1097/00004647-200106000-00006
发表时间：
2001-06-01
影响因子：
6.3
作者：
Beech, JS;Reckless, J;Menon, DK
通讯作者：
Menon, DK
影响因子：
11.2
作者：
Arumugam, Thiruma V.;Phillips, Terry M.;Cheng, Aiwu;Morrell, Christopher H.;Mattson, Mark P.;Wan, Ruiqian
通讯作者：
Wan, Ruiqian