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

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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.

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Authors and Affiliations

  1. Institute of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China

    Lang Zhang, Yu-Hong Jing, Shao-Yu Wang, Yan-Feng Song & Jie Yin

  2. Key Laboratory of Digestive System Tumors of Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, 730030, China

    Lang Zhang & Yu-Min Li

  3. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China

    Yu-Hong Jing

  4. Division of Radiology, Tumor Hospital of Gansu, Lanzhou, 730050, China

    Shao-Yu Wang

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  1. Lang Zhang
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  2. Yu-Min Li
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  3. Yu-Hong Jing
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Correspondence to Yu-Hong Jing.

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Zhang, L., Li, YM., Jing, YH. et al. Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury. Neurosci. Bull. 29, 311–320 (2013). https://doi.org/10.1007/s12264-013-1342-y

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  • DOI: https://doi.org/10.1007/s12264-013-1342-y

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