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

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

Research output: Research - peer-reviewArticle

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+CD45int 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.

LanguageEnglish (US)
Article number151
JournalJournal of Neuroinflammation
Volume14
Issue number1
DOIs
StatePublished - Jul 28 2017

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Reperfusion Injury
Brain Ischemia
Proteins
etifoxine
Middle Cerebral Artery Infarction
Reperfusion
Brain Injuries
Ischemia
Microglia
Therapeutics
Colony-Stimulating Factor Receptors
Brain Infarction
Macrophage Colony-Stimulating Factor
Mitochondrial Membranes
Nitric Oxide Synthase Type II
Protein Transport
Interleukin-1beta
Neuroglia
Cause of Death
Interleukin-6

Keywords

  • Cerebral ischemia
  • Etifoxine
  • Neuroinflammation
  • TSPO

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury. / Li, Han Dong; Li, Minshu; Shi, Elaine; Jin, Wei Na; Wood, Kristofer; Gonzales, Rayna; Liu, Qiang.

In: Journal of Neuroinflammation, Vol. 14, No. 1, 151, 28.07.2017.

Research output: Research - peer-reviewArticle

Li, Han Dong ; Li, Minshu ; Shi, Elaine ; Jin, Wei Na ; Wood, Kristofer ; Gonzales, Rayna ; Liu, Qiang. / A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury. In: Journal of Neuroinflammation. 2017 ; Vol. 14, No. 1.
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