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Journal of Neuroinflammation

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Open Access 01-12-2017 | Research

A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury

Authors: Han-Dong Li, Minshu Li, Elaine Shi, Wei-Na Jin, Kristofer Wood, Rayna Gonzales, Qiang Liu

Published in: Journal of Neuroinflammation | Issue 1/2017

Abstract

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-1β, interleukin-6, tumor necrosis factor-α, 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.

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Title: A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury
Authors: Han-Dong Li
Minshu Li
Elaine Shi
Wei-Na Jin
Kristofer Wood
Rayna Gonzales
Qiang Liu
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-017-0921-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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