Abstract:

Objective   To investigate the effects of acute hyperglycemia on ischemia-induced blood-brain barrier (BBB) impairment and the mechanism involved．Methods   Wistar rats were randomly divided into sham operation group, normoglycemia (NG) group, hyperglycemia (HG) group  and glycyrrhizic acid (GL) intervention (NG+GL, HG+GL)groups. Ischemia was induced by 90 minutes middle cerebral artery occlusion. Western blotting was used to detect the release of high mobility group box 1 (HMGB1) in cerebrospinal fluid, and BBB permeability was evaluated by Evan′s blue (EB) leakage. Brain edema, infarction volume, neurological deficit scores were evaluated after operation. Results   Hyperglycemia significantly enhanced the release of HMGB1 in cerebrospinal fluid, compared with the NG group (P<0.01). Meanwhile, Hyperglycemia significantly increased the brain edema and the infarction volume (P<0.01) and worsened the neurological deficit (P<0.05). Inhibition of HMGB1 with 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 HMGB1 may contribute to the hyperglycemia-exacerbated BBB damage. Inhibiting HMGB1 may protect the BBB from the hyperglycemia-exacerbated damage.

Key words: High mobility group box 1; Blood-brain barrier;  Glycyrrhizic acid; Cerebral ischemia; Rats