Microglia in ischemic brain injury.
Microglia in ischemic brain injury.
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DOI：
10.2217/fnl.10.1
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发表时间：
2010-03-01
期刊：
影响因子：
1.3
通讯作者：
Möller T
中科院分区：
文献类型：
--
作者：
Weinstein JR;Koerner IP;Möller T
小胶质细胞是中枢神经系统的免疫细胞，在健康的大脑中是活跃的传感器，在病理条件下是多功能的效应器。脑缺血诱导强烈的神经炎性反应，包括多种内源性CNS细胞类型（星形胶质细胞、神经元和小胶质细胞）的基因表达谱和表型的显著变化，以及来自外周的白细胞（中性粒细胞、巨噬细胞和T细胞）的流入。许多分子和条件可以触发测量小胶质细胞向警觉或反应状态的小胶质细胞的转化。在这里，我们回顾了最近的发展，在体外和体内缺血的实验环境中的小胶质细胞激活的文献。我们还提出了来自我们自己实验室的新数据，证明了体外缺血条件对小胶质细胞表型和基因组谱的直接影响。特别是，我们专注于特定的分子信号系统，如缺氧诱导因子-1和Toll样受体-4，在调节小胶质细胞反应在这种情况下的作用。然后，我们回顾了组织学和新的放射学数据，证实了小胶质细胞激活在人类缺血性卒中中的关键作用。我们还讨论了急性缺血性卒中中小胶质细胞的药理学和分子靶向治疗的最新进展。最后，我们探讨了最近关于缺血预适应的研究如何增加了人们对先发制人地靶向小胶质细胞激活以降低卒中严重程度的兴趣。
Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity.