PMID- 19917131 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121002 LR - 20220310 IS - 1750-1326 (Electronic) IS - 1750-1326 (Linking) VI - 4 DP - 2009 Nov 16 TI - Does neuroinflammation fan the flame in neurodegenerative diseases? PG - 47 LID - 10.1186/1750-1326-4-47 [doi] AB - 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. FAU - Frank-Cannon, Tamy C AU - Frank-Cannon TC AD - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, USA. malu.tansey@emory.edu. FAU - Alto, Laura T AU - Alto LT FAU - McAlpine, Fiona E AU - McAlpine FE FAU - Tansey, Malu G AU - Tansey MG LA - eng GR - R01 NS049433/NS/NINDS NIH HHS/United States GR - R01 NS049433-04/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20091116 PL - England TA - Mol Neurodegener JT - Molecular neurodegeneration JID - 101266600 PMC - PMC2784760 EDAT- 2009/11/18 06:00 MHDA- 2009/11/18 06:01 PMCR- 2009/11/16 CRDT- 2009/11/18 06:00 PHST- 2009/09/03 00:00 [received] PHST- 2009/11/16 00:00 [accepted] PHST- 2009/11/18 06:00 [entrez] PHST- 2009/11/18 06:00 [pubmed] PHST- 2009/11/18 06:01 [medline] PHST- 2009/11/16 00:00 [pmc-release] AID - 1750-1326-4-47 [pii] AID - 10.1186/1750-1326-4-47 [doi] PST - epublish SO - Mol Neurodegener. 2009 Nov 16;4:47. doi: 10.1186/1750-1326-4-47.