Article

Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: Underlying mechanisms

CNS Inflammation Group, School of Biological Sciences, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK.
Neuroscience (Impact Factor: 3.33). 08/2008; 158(3):1062-73. DOI: 10.1016/j.neuroscience.2008.07.031
Source: PubMed

ABSTRACT 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.

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    • "It has been demonstrated that the release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), increases following surgery (4,5). These pro-inflammatory cytokines may trigger broad neuroinflammation in the brain (6). Thus, the effective inhibition of the activity of signaling pathways involved in inflammation and pro-inflammatory cytokine expression shows promise for the prevention and treatment for POCD. "
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