Microglia and neurodegeneration: The role of systemic inflammation
Article first published online: 6 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Special Issue: Microglia
Volume 61, Issue 1, pages 71–90, January 2013
How to Cite
Cunningham, C. (2013), Microglia and neurodegeneration: The role of systemic inflammation. Glia, 61: 71–90. doi: 10.1002/glia.22350
- Issue published online: 14 NOV 2012
- Article first published online: 6 JUN 2012
- Manuscript Accepted: 17 APR 2012
- Manuscript Received: 20 FEB 2012
- Wellcome Trust
- phenotype switching;
- Alzheimer's disease;
- Parkinson's disease;
It is well accepted that CNS inflammation has a role in the progression of chronic neurodegenerative disease, although the mechanisms through which this occurs are still unclear. The inflammatory response during most chronic neurodegenerative disease is dominated by the microglia and mechanisms by which these cells contribute to neuronal damage and degeneration are the subject of intense study. More recently it has emerged that systemic inflammation has a significant role to play in the progression of these diseases. Well-described adaptive pathways exist to transduce systemic inflammatory signals to the brain, but activation of these pathways appears to be deleterious to the brain if the acute insult is sufficiently robust, as in severe sepsis, or sufficiently prolonged, as in repeated stimulation with robust doses of inflammogens such as lipopolysaccharide (LPS). Significantly, moderate doses of inflammogens produce new pathology in the brain and exacerbate or accelerate features of disease when superimposed upon existing pathology or in the context of genetic predisposition. It is now apparent in multiple chronic disease states, and in ageing, that microglia are primed by prior pathology, or by genetic predisposition, to respond more vigorously to subsequent inflammatory stimulation, thus transforming an adaptive CNS inflammatory response to systemic inflammation, into one that has deleterious consequences for the individual. In this review, the preclinical and clinical evidence supporting a significant role for systemic inflammation in chronic neurodegenerative diseases will be discussed. Mechanisms by which microglia might effect neuronal damage and dysfunction, as a consequence of systemic stimulation, will be highlighted. © 2012 Wiley Periodicals, Inc.