Background: 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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/625392 |
| Date | 28 July 2017 |
| Creators | Li, Han-Dong, Li, Minshu, Shi, Elaine, Jin, Wei-Na, Wood, Kristofer, Gonzales, Rayna, Liu, Qiang |
| Contributors | Univ Arizona, Coll Med, Dept Basic Med Sci |
| Publisher | BIOMED CENTRAL LTD |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License. |
| Relation | http://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0921-7 |
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