Acute Hyperglycemia Worsens Ischemic Stroke-induced Brain Damage Via High Mobility Group Box-1in Rats

Background:Stroke is a rare and common disease, and which caused by middle cerebral artery infarction cerebral ischemia is particularly common.Ischemic Cerebral Vesscular Disease has high mortality and morbidity.Recanalization of blood vessel in the treatment of ischemic cerebral apoplexy is particularly important for ischemic brain tissue repair injury, but the ischemia-reperfusion injury was by far the most concern problem.Clinical studies have found that hyperglycemia is a common phenomenon among ischemic cerebral patients, what cause high blood sugar are still not fully elucidated, mostly considered diabetes or irritable response performance, hyperglycemia may increase mortality and morbidity in patients with cerebral stroke and its influence nerve functional recovery, has become a prediction of the prognosis of patients with ischemic stroke an independent index.However, the relationship of hyperglycemia and CIRI is unclear nowadays, whether hyperglycemia itself may induce CIRI and worsen it? Or just an indicator of prognosis of ICS are still unclear.And hyperglycemia is aggravating CIRI precise mechanism has not yet been elucidated.In the normal brain tissue, most brain cells HMGB1lower expression.During cerebral ischemia, lots of HMGB1is released into the extracellular immediately, the extracellular HMGBI as an important medium of inflammation and maintain and extend the inflammation. With the development of nerve inflammation, the close connection of the blood-brain barrier formed By brain astrocytes and vascular endothelial cells is damaged, which bring cerebral edema..Though, the role of HMGB1in ischemic brain injury mechanism of the study is more, however, its role in acute hyperglycemia aggravate ischemic brain damage mechanism is less reported.Objective:To set up the model for MCAO,to explore the influnce and machiniamof the extracellular HMGB1during hyperglycemic stroke.Methods:60male wistar rats were assigned to sham operation group,normoglycemia(NG)group,hyperglycemia (HG)group,and glycyrrhizic acid (GL) intervention (NG+GL,HG+GL)groups.ischemia was induced by90minutes after MCAO.westblot was used to detected the release of hogh mobility group box-1(HMGB1)in cerebro spinal fluid at2h and4h after reperfusion.,and BBB permeability was evaluated by Evan’s blue (EB) leakage at4h after reperfusion,By westblot testing HMGB1and Occludin content in brain tissue at4h after reperfusion brain edama,infaraction volume,neuroiogical deficit scores were evaluated after operation at24h after reperfusion.Results:Compared with the NG roup(P<0.01).meanwhile,hyperglycemia signnificantly increased the brain edema and the infartion volume(P<0.01)and worsened the neurological deficit(P<0.05),hyperglycemia significantly enhanced there lease of HMGB1incerebrospinal fluid;Occludin levels in the brain tissue decreased obviously Inhibition of HMGB1with GL significantly reduced EB leakage,brain edema,infarction volume,and neurological deficit(P<0.01)Conclusion:In transient middle cerebral artery occlusion,the increased release of HMGB1may contribute to the hyperglycemia eaacerbated BBB damage.In hibiting HMGB1may protect the BBB from the hyperglycemia exacerbated damage; NG+GL group compared with NG group, there are obviously improved.