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Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats

机译:高压氧预处理可减轻大鼠短暂MCAO后高血糖增强的出血转化

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Background Hemorrhagic transformation (HT) can be a devastating complication of ischemic stroke. Hyperbaric oxygen preconditioning (HBO-PC) has been shown to improve blood-brain barrier (BBB) permeability in stroke models. The purpose of this study is to examine whether HBO-PC attenuates HT after focal cerebral ischemia, and to investigate whether the mechanism of HBO-PC against HT includes up-regulation of antioxidants in hyperglycemic rats. Methods Male Sprague-Dawley rats (280-320 g) were divided into the following groups: sham, middle cerebral artery occlusion (MCAO) for 2 h, and MCAO treated with HBO-PC. HBO-PC was conducted giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at every 24 h interval for 5 days. At 24 h after the last session of HBO-PC, rats received an injection of 50% glucose (6 ml/kg intraperitoneally) and were subjected to MCAO 15 min later. At 24 h after MCAO, neurological behavior tests, infarct volume, blood-brain barrier permeability, and hemoglobin content were measured to evaluate the effect of HBO-PC. Western blot analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was evaluated at multiple time-points before and after MCAO. Results HBO-PC improved neurological behavior test, and reduced infarction volume, HT and Evans blue extravasation in the ipsilateral hemisphere at 24 h after MCAO. Western blot analysis failed to demonstrate up-regulation of Nrf2 in HBO-PC group before and after MCAO. Paradoxically, HBO-PC decreased HO-1 expression at 24 h after MCAO, as compared with htMCAO group. Conclusions HBO-PC improved neurological deficits, infarction volume, BBB disruption, and HT after focal cerebral ischemia. However, its mechanism against focal cerebral ischemia and HT may not include activation of Nrf2 and subsequent HO-1 expression.
机译:背景出血性转化(HT)可能是缺血性中风的毁灭性并发症。高压氧预处理(HBO-PC)已显示可改善中风模型的血脑屏障(BBB)渗透性。这项研究的目的是检查HBO-PC是否能在局灶性脑缺血后减弱HT,并研究HBO-PC对抗HT的机制是否包括高血糖大鼠中抗氧化剂的上调。方法将雄性Sprague-Dawley大鼠(280-320 g)分为假手术,脑中动脉闭塞(MCAO)2小时和HBO-PC处理MCAO。进行HBO-PC,在2.5 atm绝对压力(ATA)下提供100%的氧气,每隔24小时间隔1小时,持续5天。在最后一次HBO-PC后24小时,大鼠接受50%葡萄糖注射(腹膜内注射6 ml / kg),并在15分钟后接受MCAO。 MCAO后24小时,通过神经行为学测试,梗塞体积,血脑屏障通透性和血红蛋白含量来评估HBO-PC的效果。在MCAO之前和之后的多个时间点评估了核因子红系2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的蛋白质印迹分析。结果MCAO后24 h,HBO-PC改善了神经行为学测试,并减少了同侧半球的梗死体积,HT和伊文思蓝外渗。 Western blot分析未能证明MCAO前后HBO-PC组Nrf2的上调。与htMCAO组相比,HBO-PC在MCAO后24 h降低HO-1表达。结论HBO-PC可改善局灶性脑缺血后的神经功能缺损,梗死体积,BBB破坏和HT。但是,其对抗局灶性脑缺血和HT的机制可能不包括Nrf2的激活和随后的HO-1表达。

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