Teeling J L, Perry V H
CNS Inflammation Group, School of Biological Sciences, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK.
Neuroscience. 2009 Feb 6;158(3):1062-73. doi: 10.1016/j.neuroscience.2008.07.031. Epub 2008 Jul 25.
We have all at some time experienced the non-specific symptoms that arise from being ill following a systemic infection. These symptoms, such as fever, malaise, lethargy and loss of appetite are often referred to as "sickness behavior" and are a consequence of systemically produced pro-inflammatory mediators. These inflammatory mediators signal to the brain, leading to activation of microglial cells, which in turn, signal to neurons to induce adaptive metabolic and behavioral changes. In normal healthy persons this response is a normal part of our defense, to protect us from infection, to maintain homeostasis and causes no damage to neurons. However, in animals and patients with chronic neurodegenerative disease, multiple sclerosis, stroke and even during normal aging, systemic inflammation leads to inflammatory responses in the brain, an exaggeration of clinical symptoms and increased neuronal death. These observations imply that, as the population ages and the number of individuals with CNS disorders increases, relatively common systemic infections and inflammation will become significant risk factors for disease onset or progression. In this review we discuss the underlying mechanisms responsible for sickness behavior induced by systemic inflammation in the healthy brain and how they might be different in individuals with CNS pathology.
我们都曾在某个时候经历过全身性感染后生病时出现的非特异性症状。这些症状，如发烧、不适、嗜睡和食欲不振，通常被称为“疾病行为”，是全身产生的促炎介质的结果。这些炎症介质向大脑发出信号，导致小胶质细胞激活，而小胶质细胞又向神经元发出信号，诱导适应性代谢和行为变化。在正常健康人身上，这种反应是我们防御机制的正常组成部分，能保护我们免受感染、维持体内平衡，且不会对神经元造成损害。然而，在患有慢性神经退行性疾病、多发性硬化症、中风的动物和患者中，甚至在正常衰老过程中，全身性炎症会导致大脑中的炎症反应，临床症状加重，神经元死亡增加。这些观察结果表明，随着人口老龄化以及中枢神经系统疾病患者数量的增加，相对常见的全身性感染和炎症将成为疾病发作或进展的重要危险因素。在这篇综述中，我们讨论了健康大脑中由全身性炎症诱导的疾病行为的潜在机制，以及它们在患有中枢神经系统病理学疾病的个体中可能有何不同。
