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.
Keywords: 2,3,5-triphenyletetrazolium chloride; BBB; Blood–brain barrier; CSF; Cerebral ischemia; Glycyrrhizin; HMGB1; Hyperglycemia; MCAO; Rat; TTC; blood–brain barrier; cerebrospinal fluid; high mobility group box-1; middle cerebral artery occlusion.
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