Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats.
Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats.
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DOI：
10.1186/2045-9912-2-9
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发表时间：
2012-04-11
影响因子：
2.9
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Soejima Y;Ostrowski RP;Manaenko A;Fujii M;Tang J;Zhang JH
出血性转化（HT）可能是缺血性中风的一种毁灭性并发症。在脑卒中模型中，高压氧预处理（HBO-PC）已被证明可以改善血脑屏障（BBB）的通透性。本研究旨在探讨HBO-PC是否能减轻局灶性脑缺血后的HT，并探讨HBO-PC抗HT的机制是否包括上调高血糖大鼠抗氧化剂。雄性Sprague-Dawley大鼠（280 ~ 320 g）分为假手术组、大脑中动脉闭塞组（MCAO） 2 h组和HBO-PC处理的MCAO组。HBO-PC在绝对2.5 atm （ATA）下给予100%氧气，每24 h间隔1 h，连续5天。最后一次HBO-PC后24 h，大鼠腹腔注射50%葡萄糖（6 ml/kg）， 15 min后进行MCAO。在MCAO后24 h，通过神经行为学测试、梗死面积、血脑屏障通透性和血红蛋白含量来评价HBO-PC的效果。在MCAO前后多个时间点进行核因子-红细胞2相关因子2 （Nrf2）和血红素加氧酶-1 （HO-1）的Western blot分析。HBO-PC改善了神经行为测试，减少了MCAO后24 h同侧半球梗死体积、HT和Evans蓝外渗。Western blot分析未发现HBO-PC组在MCAO前后Nrf2表达上调。与htMCAO组相比，HBO-PC在MCAO后24小时降低了HO-1的表达。HBO-PC改善局灶性脑缺血后的神经功能缺损、梗死体积、血脑屏障破坏和HT。然而，其抗局灶性脑缺血和HT的机制可能不包括Nrf2的激活和随后HO-1的表达。
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. 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. 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. 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.