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1. Glibenclamide Improves Survival and Neurological Outcome after Cardiac Arrest in Rats | |||
Huang Kaibin,Gu Yong,Hu Yafang,Ji Zhong,Wang Shengnan,Lin Zhenzhou,Li Xing,Xie Zuoshan,Pan Suyue | |||
Clinical Medicine 21 May 2016 | |||
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Abstract: Objectives: Glibenclamide (GBC) confers neuroprotection in animal models as well as retrospective clinical studies. This study determines whether GBC improves outcome after cardiac arrest in rats. Methods and Results: Male Sprague-Dawley rats successfully resuscitated from 8-min asphyxial cardiac arrest were randomized to GBC or Vehicle group. Rats in the GBC group were intraperitoneally administered GBC with a loading dose of 10 μg/kg at 10 mins and a maintenance dose of 1.2 μg at 6, 12, 18, and 24 hrs after return of spontaneous circulation (ROSC), while rats in the Vehicle group received equivalent volume of vehicle solution. Survival was recorded every day and neurologic deficit scores were assessed at 24, 48, 72 hrs and 7 days after ROSC (n = 22 in each group). Results showed that GBC treatment increased 7-day survival rate, reduced neurologic deficit scores and prevented neuronal loss in the hippocampal CA1 region. To investigate the neuroprotective effects of GBC in acute phase, we observed neuronal injury at 24 hrs after ROSC, and found that GBC significantly decreased the rate of neuronal necrosis and apoptosis. In addition, GBC reduced the mRNA expression of tumor necrosis factor α and monocyte chemoattractant protein-1 in the cortex after ROSC. Furthermore, the sulfonylurea receptor 1 and transient receptor potential M4 heteromers, the putative therapeutic targets of GBC, were up-regulated after cardiac arrest and cardiopulmonary resuscitation, indicating that they might be involved in neuroprotective effect of GBC. Conclusions: GBC treatment substantially improved survival and neurological outcome throughout a 7-day period after ROSC. The salutary effects of GBC was associated with suppression of neuronal necrosis and apoptosis, as well as inflammation in the brain. | |||
TO cite this article:Huang Kaibin,Gu Yong,Hu Yafang, et al. Glibenclamide Improves Survival and Neurological Outcome after Cardiac Arrest in Rats[OL].[21 May 2016] http://en.paper.edu.cn/en_releasepaper/content/4693594 |
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