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. 2013 May 7;29(3):311–320. doi: 10.1007/s12264-013-1342-y

Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury

Lang Zhang 11342,21342, Yu-Min Li 21342, Yu-Hong Jing 11342,31342,✉, Shao-Yu Wang 11342,41342, Yan-Feng Song 11342, Jie Yin 11342
PMCID: PMC5561849  PMID: 23650049

Abstract

Accumulating evidence has suggested that the gap junction plays an important role in the determination of cerebral ischemia, but the underlying mechanisms remain to be elucidated. In this study, we assessed the effect of a gap-junction blocker, carbenoxolone (CBX), on ischemia/reperfusion-induced brain injury and the possible mechanisms. By using the transient cerebral ischemia model induced by occlusion of the middle cerebral artery for 30 min followed by reperfusion for 24 h, we found that pre-administration of CBX (25 mg/kg, intracerebroventricular injection, 30 min before cerebral ischemic surgery) diminished the infarction size in rats. And this was associated with a decrease of reactive oxygen species generation and inhibition of the activation of astrocytes and microglia. In PC12 cells, H2O2 treatment induced more coupling and apoptosis, while CBX partly inhibited the opening of gap junctions and improved the cell viability. These results suggest that cerebral ischemia enhances the opening of gap junctions. Blocking the gap junction with CBX may attenuate the brain injury after cerebral ischemia/reperfusion by partially contributing to amelioration of the oxidative stress and apoptosis.

Keywords: gap junction communication, cerebral ischemia, reactive oxygen species

Footnotes

These authors contributed equally to this work.

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