A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury
AffiliationUniv Arizona, Coll Med, Dept Basic Med Sci
MetadataShow full item record
PublisherBIOMED CENTRAL LTD
CitationA translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury 2017, 14 (1) Journal of Neuroinflammation
JournalJournal of Neuroinflammation
Rights© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBackground: Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion. Methods: We used a mouse model of middle cerebral artery occlusion (MCAO) to examine the therapeutic potential and mechanisms of neuroprotection by etifoxine. Results: TSPO was upregulated in Iba1(+) or CD11b(+) CD45(int) cells from mice subjected to MCAO and reperfusion. Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or 90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the ischemic brain. In addition, etifoxine treatment led to decreased expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase by microglia. Notably, the benefit of etifoxine against brain infarction was ablated in mice depleted of microglia using a colony-stimulating factor 1 receptor inhibitor. Conclusions: These findings indicate that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury after ischemia/reperfusion. The therapeutic potential of targeting TSPO requires further investigations in ischemic stroke.
VersionFinal published version
SponsorsAmerican Heart Association [16SDG27250236]; National Science Foundation of China ; Ministry of Human Resources and Social Security of China ; Tianjin Education Commission Foundation [14JCYBJC42000]; Tianjin Medical University Graduate Student Innovation Foundation [YJSCX201718]