Relationship Between Hematoma Expansion Induced by Hypertension and Hyperglycemia and Blood-brain Barrier Disruption in Mice and Its Possible Mechanism:Role of Aquaporin-4 and Connexin43

We aimed to select an optimized hematoma expansion(HE)model and investigate the possible mechanism of blood-brain barrier(BBB)damage in mice.The results showed that HE occurred in the group with hypertension combined with hyperglycemia(HH-HE)from3 to 72 h after intracerebral hemorrhage;this was accompanied by neurological deficits and hardly influenced the survival rate.The receiver operating characteristic curve suggested the criterion for this model was hematoma volume expansion≥45.0%.Meanwhile,HH-HE aggravated BBB disruption.A protector of the BBB reduced HH-HE,while a BBB disruptor induced a further HH-HE.Aquaporin-4(AQP4)knock-out led to larger hematoma volume and more severe BBB disruption.Furthermore,hematoma volume and BBB disruption were reduced by multiple connexin43(Cx43)inhibitors in the wild-type group but not in the AQP4 knock-out group.In conclusion,the optimized HE model is induced by hypertension and hyperglycemia with the criterion of hematoma volume expanding≥45.0%.HH-HE leads to BBB disruption,which is dependent on AQP4 and Cx43.