1Institute of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000,
China
2Key Laboratory of Digestive System Tumors of Gansu Province, The Second Hospital of Lanzhou University, Lanzhou
730030, China
3Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou
University, Lanzhou 730000, China
4Division of Radiology, Tumor Hospital of Gansu, Lanzhou 730050, China
#These authors contributed equally to this work.

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

[SpringerLink]