Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats
Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats
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DOI：
10.1016/j.brainres.2013.08.057
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发表时间：
2013-10-16
期刊：
影响因子：
2.9
通讯作者：
Yuan, Zhongrui
中科院分区：
文献类型：
--
作者：
Huang, Jingyang;Liu, Baoyi;Yuan, Zhongrui
高血糖对缺血性脑卒中的预后有不利影响。细胞外HMGB1在脑缺血后脑损伤中起加重作用。本研究的目的是确定细胞外HMGB1是否参与高血糖卒中时缺血性损伤的恶化。雄性Wistar大鼠大脑中动脉闭塞（MCAO） 90 min，再灌注。注射50%葡萄糖诱导急性高血糖。大鼠接受甘草酸，一种特异性HMGB1抑制剂或载体。再灌注后2、4 h检测脑脊液和脑实质中HMGB-1的含量。观察mcao后24 h的神经功能缺损、梗死体积和脑水肿情况，再灌注后4 h检测血脑屏障（BBB）破坏情况和紧密连接蛋白Occludin的表达。高血糖增强了缺血脑组织HMGB1的早期释放，并伴有梗死体积增加、神经功能缺损、脑水肿和血脑屏障破坏。甘草酸通过降低缺血半球紧密连接蛋白Occludin的降解，减轻了高血糖大鼠梗死体积加重、神经功能缺损、脑水肿和血脑屏障破坏。总之，HMGB1的细胞外早期释放增强可能是高血糖卒中期间缺血性损伤恶化的重要机制，特别是早期血脑屏障破坏。HMGB1抑制剂甘草酸是高血糖性卒中的潜在治疗选择。(C) 2013 Elsevier B.V.版权所有
Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke. (C) 2013 Elsevier B.V. All rights reserved.