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原发性脑出血治疗的新视野:来自临床前研究的经验

New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies.

作者信息

Aronowski Jaroslaw, Hall Christiana E

机构信息

Stroke Program, Department of Neurology, University of Texas-Houston Medical School, Houston, TX 77030, USA.

出版信息

Neurol Res. 2005 Apr;27(3):268-79. doi: 10.1179/016164105X25225.

Abstract

Intracerebral hemorrhage (ICH) remains a major medical problem, for which there is no effective treatment. However, extensive experimental and clinical research carried out in recent years has brought to light new exciting ideas for novel potential treatments. First, it was well documented that the management of hypertension helps to prevent new and recurrent ICH. Also, development of new guidelines for management of hypertension after the onset of the ICH may help in more effective ICH treatment. Existing contemporary data collected from preclinical studies indicates that ICH-induced inflammation represents a key factor leading to secondary brain damage, suggesting that some anti-inflammatory approaches can be used to treat hemorrhagic stroke. In this article, beyond discussing implications related to hypertension, we will summarize important (but not all) new discoveries connecting the role of inflammation to ICH pathology. Selected aspects of inflammatory response including the role of cytokines, transcription factor nuclear factor-kB, microglia activation, astrogliosis, and complement activation will be introduced. We will also discuss the role for reactive oxygen species and metalloproteinases in ICH pathogenesis and introduce basic knowledge on the nature of ICH-induced cell death including apoptosis. Potential targets for intervention and translation will be discussed.

摘要

脑出血(ICH)仍然是一个重大的医学问题,目前尚无有效的治疗方法。然而,近年来进行的大量实验和临床研究为新型潜在治疗方法带来了令人兴奋的新想法。首先,有充分的文献记载,控制高血压有助于预防新的和复发性脑出血。此外,制定脑出血发作后高血压管理的新指南可能有助于更有效地治疗脑出血。从临床前研究收集的现有当代数据表明,脑出血引发的炎症是导致继发性脑损伤的关键因素,这表明一些抗炎方法可用于治疗出血性中风。在本文中,除了讨论与高血压相关的影响外,我们还将总结将炎症作用与脑出血病理联系起来的重要(但并非全部)新发现。将介绍炎症反应的选定方面,包括细胞因子的作用、转录因子核因子-κB、小胶质细胞活化、星形胶质细胞增生和补体激活。我们还将讨论活性氧和金属蛋白酶在脑出血发病机制中的作用,并介绍关于脑出血诱导的细胞死亡性质(包括凋亡)的基础知识。将讨论潜在的干预和转化靶点。

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