Does neuroinflammation fan the flame in neurodegenerative diseases?
Does neuroinflammation fan the flame in neurodegenerative diseases?
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DOI：
10.1186/1750-1326-4-47
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发表时间：
2009-11-16
影响因子：
15.1
通讯作者：
Tansey MG
中科院分区：
文献类型：
--
作者：
Frank-Cannon TC;Alto LT;McAlpine FE;Tansey MG
虽然外周免疫进入中枢神经系统（CNS）受到限制和严格控制，但CNS能够对各种损伤产生动态免疫和炎症反应。感染、创伤、中风、毒素和其他刺激能够在CNS内产生先天免疫系统的立即和短暂的激活。这种急性神经炎症反应包括激活常驻免疫细胞（小胶质细胞），导致吞噬细胞表型和释放炎症介质，如细胞因子和趋化因子。虽然急性损伤可能引发氧化和亚硝化应激，但它通常是短暂的，不太可能对长期神经元存活有害。相比之下，慢性神经炎症是一种长期存在的，通常是自我延续的神经炎症反应，在初始损伤或损伤后持续很长时间。慢性神经炎症不仅包括小胶质细胞的长期激活和随后的炎症介质的持续释放，而且还包括由此产生的氧化和亚硝化应激的增加。炎症介质的持续释放使炎症循环持续，激活额外的小胶质细胞，促进其增殖，并导致炎症因子的进一步释放。神经退行性CNS病症，包括多发性硬化（MS）、阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）、肌萎缩侧索硬化（ALS）、tau蛋白病和年龄相关性黄斑变性（ARMD），与慢性神经炎症和几种细胞因子水平升高相关。在这里，我们审查的急性和慢性炎症反应的中枢神经系统的标志，小胶质细胞激活的原因是不同的刺激，可能会促进或损害神经元的生存，和流行病学，药理学和遗传学证据牵连神经炎症的病理生理学的几种神经退行性疾病的汇聚点。
While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.
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影响因子：
5.3
作者：
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通讯作者：
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