Role of Glia in CNS Inflammation

Abstract:

Inflammation is being increasingly recognized to play pathogenic roles in diverse neurological conditions and diseases including not only primary inflammatory diseases such as multiple sclerosis and HIV dementia but also primary degenerative disorders such as Alzheimer's and Parkinson's, as well as in brain injuries resulting from stroke and trauma. In the CNS, microglia, the resident macrophages, and astrocytes, the major endogenous glial cell type, together represent the main immunocompetent cell system that responds to any number of brain injuries, infections, and disease conditions, thereby mediating the local inflammatory response, i.e., “neuroinflammation.” The stimuli that activate these cells come in the form of microbial products, cytokines, products released by injured neurons, and disease-specific abnormal molecules. Activated glial cells in turn release several potentially neurotoxic mediators including cytokines, chemokines, reactive oxygen species, and nitric oxide, which target bystander neurons and oligodendrocytes. Although in acute settings, glial activation may be beneficial by clearing out debris and allowing repair to occur via released trophic factors, situations of their chronic response would entail deleterious neurodegenerative outcome. A better understanding of these processes would help devise appropriate neuroinflammation-targeted interventions against neurological diseases.

In this chapter, we review the mechanisms of glial cell activation by different stimuli, associated inflammatory signaling pathways, and the induced release of inflammatory mediators. This is followed by a review of the current literature highlighting the roles of glial cells in some of the common neurodegenerative and inflammatory diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion disease, multiple sclerosis, and HIV encephalitis.