Inflammation and neurovascular changes in amyotrophic lateral sclerosis
Inflammation and neurovascular changes in amyotrophic lateral sclerosis
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DOI：
10.1016/j.mcn.2012.10.008
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发表时间：
2013-03-01
影响因子：
3.5
通讯作者：
Turner, M. R.
中科院分区：
文献类型：
--
作者：
Evans, M. C.;Couch, Y.;Turner, M. R.
神经炎症是包括肌萎缩侧索硬化（ALS）在内的许多神经退行性疾病发病机制中的重要因素。在不同的时间点，星形胶质细胞和小胶质细胞被显著激活，产生神经保护或促炎分子，其可以分别降低或增加初级运动神经元变性的速率。最近的研究表明，这种神经炎性成分受到外周免疫系统的影响;特别是T淋巴细胞能够进入大脑和脊髓实质，在那里它们与驻留的小胶质细胞相互作用，诱导它们采用M1（细胞毒性）或M2（保护性）表型，这取决于疾病的阶段。清楚地了解发生的变化，使外周和中枢免疫反应之间的相互作用将是至关重要的，在任何试图通过神经炎症机制操纵疾病的过程。然而，我们对内皮细胞变化的理解，这有助于外周免疫细胞浸润到大脑和脊髓，仍然处于起步阶段。然而，有迹象表明，细胞粘附分子的上调能够阻止循环中的白细胞并促进渗出到脑实质中。此外，紧密连接蛋白似乎被下调，导致血管通透性增加，这种效应在疾病过程后期被血管损伤放大。这篇综述总结了我们目前对ALS中神经炎症、外周免疫参与和内皮变化的认识。这篇文章是题为“神经变性和神经功能障碍中的神经炎症”的特刊的一部分。(c)2012年由Elsevier Inc.出版
Neuroinflammation in now established as an important factor in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). At various time points, astrocytes and microglia are markedly activated, either producing neuroprotective or pro-inflammatory molecules, which can decrease or increase the rate of primary motor neuron degeneration respectively. Recent research has shown that this neuroinflammatory component is affected by the peripheral immune system; T lymphocytes in particular are able to cross into the brain and spinal cord parenchyma, where they interact with resident microglia, either inducing them to adopt an M1 (cytotoxic) or M2 (protective) phenotype, depending on the stage of disease. Clearly understanding the changes that occur to allow the interaction between peripheral and central immune responses will be essential in any attempt to manipulate the disease process via neuroinflammatory mechanisms. However, our understanding of the endothelial changes, which facilitate the infiltration of peripheral immune cells into the brain and spinal cord, is still in its infancy. There are suggestions, though, of up-regulation of cellular adhesion molecules, which are able to arrest circulating leukocytes and facilitate diapedesis into the brain parenchyma. In addition, tight junction proteins appear to be down-regulated, leading to an increase in vascular permeability, an effect that is amplified by vascular damage late in the disease process. This review summarises our current knowledge regarding neuroinflammation, peripheral immune involvement, and endothelial changes in ALS. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. (c) 2012 Published by Elsevier Inc.