title: Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors.
abstract: Stroke is the leading cause of disability in adults. Drug treatments that target stroke-induced pathological mechanisms and promote recovery are desperately needed. In the brain, an ischemic event triggers major inflammatory responses that are mediated by the resident microglial cells. In this review, we focus on the microglia activation after ischemic brain injury as a target of immunomodulatory therapeutics. We divide the microglia-mediated events following ischemic stroke into three categories: acute, subacute, and long-term events. This division encompasses the spatial and temporal dynamics of microglia as they participate in the pathophysiological changes that contribute to the symptoms and sequela of a stroke. The importance of Toll-like receptor (TLR) signaling in the outcomes of these pathophysiological changes is highlighted. Increasing evidence shows that microglia have a complex role in stroke pathophysiology, and they mediate both detrimental and beneficial effects on stroke outcome. So far, most of the pharmacological studies in experimental models of stroke have focused on neuroprotective strategies which are impractical for clinical applications. Post-ischemic inflammation is long lasting and thus, could provide a therapeutic target for novel delayed drug treatment. However, more studies are needed to elucidate the role of microglia in the recovery process from an ischemic stroke and to evaluate the therapeutic potential of modulating post-ischemic inflammation to promote functional recovery.
authors.affiliation: Institute of Biotechnology, P.O. Box 56, 00014, University of Helsinki, Finland.
authors.forename: Jenni E
authors.initials: JE
authors.lastname: Anttila
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, USA; Human Research and Engineering Directorate, US Army Research Laboratory, Aberdeen, Proving Ground, MD 21005, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Whitaker
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wires
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.affiliation: Institute of Biotechnology, P.O. Box 56, 00014, University of Helsinki, Finland. Electronic address: mikko.airavaara@helsinki.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Airavaara
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D051193:Toll-Like Receptors
keywords: NF-κB; TLR; inflammation; nuclear factor kappa B