Vimentin participates in microglia activation and neurotoxicity in cerebral ischemia.
Microglia 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.
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
Susan X
SX
Jiang
Jacqueline
J
Slinn
Amy
A
Aylsworth
Sheng T
ST
Hou
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D002469:Cell Separation; D019084:Fluorescent Antibody Technique, Indirect; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D018613:Microscopy, Confocal; D009422:Nervous System Diseases / Q000235:genetics / Q000503:physiopathology; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D015427:Reperfusion Injury / Q000473:pathology; D013752:Tetracycline / Q000494:pharmacology; D014746:Vimentin / Q000235:genetics / Q000502:physiology*
D008070:Lipopolysaccharides; D014746:Vimentin; D013752:Tetracycline