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.