Vimentin participates in microglia activation and neurotoxicity in cerebral ischemia

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DOIResolve DOI: http://doi.org/10.1111/j.1471-4159.2012.07823.x
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TypeArticle
Journal titleJournal of Neurochemistry
ISSN0022-3042
Volume122
Issue4
Pages764774; # of pages: 11
Subjectlipopolysaccharide; tumor necrosis factor; vimentin; animal cell; animal experiment; animal model; animal tissue; article; brain infarction size; brain ischemia; cell activation; cell isolation; controlled study; gene deletion; gene expression regulation; gene overexpression; immunofluorescence; in vitro study; in vivo study; microglia; mouse; neuroprotection; neurotoxicity; nonhuman; priority journal; protein analysis; protein expression; protein function; signal transduction; Animals; Blotting, Western; Brain; Brain Ischemia; Cell Separation; Fluorescent Antibody Technique, Indirect; Image Processing, Computer-Assisted; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Lipopolysaccharides; Macrophage Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Microscopy, Confocal; Nervous System Diseases; Plasmids; Reperfusion Injury; Tetracycline; Vimentin
AbstractMicroglia are the 'immune cells' of the brain and their activation plays a vital role in the pathogenesis of many neurodegenerative diseases. Activated microglia produce high levels of pro-inflammatory factors, such as TNFα, causing neurotoxicity. Here we show that vimentin played a key role in controlling microglia activation and neurotoxicity during cerebral ischemia. Deletion of vimentin expression significantly impaired microglia activation in response to LPS in vitro and transient focal cerebral ischemia in vivo. Reintroduction of the functional vimentin gene back into vimentin knockout microglia restored their response to LPS. More importantly, impairment of microglia activation significantly protected brain from cerebral ischemia-induced neurotoxicity. Collectively, we demonstrate a previously unknown function of vimentin in controlling microglia activation. Microglia activation plays an important role in many neurodegenerative diseases. Here we show that impaired vimentin expression significantly reduced microglia activation in response to LPS in vitro and cerebral ischemia in vivo. These studies demonstrate a unknown function of vimentin in controlling microglia activation and neurotoxicity during cerebral ischemia. © 2012 National Research Council Canada & The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269505
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Record identifier23ce368c-8f5d-4fc9-8fdf-b75ee8a7cbf9
Record created2013-12-12
Record modified2016-05-09
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