Nuffield Department of Clinical Neurosciences, Oxford University, UK.
Mol Cell Neurosci. 2013 Mar;53:34-41. doi: 10.1016/j.mcn.2012.10.008. Epub 2012 Oct 27.
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'.
神经炎症现在被认为是许多神经退行性疾病（包括肌萎缩侧索硬化症，ALS）发病机制中的一个重要因素。在不同的时间点，星形胶质细胞和小胶质细胞明显被激活，分别产生神经保护或促炎分子，从而分别降低或增加原代运动神经元的退化速度。最近的研究表明，这种神经炎症成分受到外周免疫系统的影响；特别是 T 淋巴细胞能够穿过血脑屏障进入脑实质和脊髓实质，在那里与驻留的小胶质细胞相互作用，根据疾病的阶段诱导它们分别采取 M1（细胞毒性）或 M2（保护）表型。清楚地理解允许外周和中枢免疫反应之间相互作用的变化，对于通过神经炎症机制来操纵疾病过程将是至关重要的。然而，我们对允许外周免疫细胞浸润脑和脊髓的内皮变化的理解仍处于起步阶段。虽然有一些迹象表明细胞黏附分子的上调，这能够阻止循环白细胞并促进其穿过脑实质。此外，紧密连接蛋白似乎被下调，导致血管通透性增加，这一效应在疾病后期过程中的血管损伤时会被放大。这篇综述总结了我们目前对 ALS 中的神经炎症、外周免疫参与和内皮变化的了解。本文是题为“神经退行性变和神经功能障碍中的神经炎症”的特刊的一部分。
