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) from 3 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.

我们的目的是选择优化的血肿扩张（HE）模型并研究小鼠血脑屏障（BBB）损伤的可能机制。结果显示，高血压合并高血糖组（HH-HE）在脑出血后3～72 h发生HE；这伴随着神经功能缺陷，几乎不影响生存率。受试者工作特征曲线表明该模型的标准是血肿体积扩张≥45.0%。同时，HH-HE 加剧了 BBB 破坏。 BBB 的保护者减少了 HH-HE，而 BBB 的破坏者则诱导了进一步的 HH-HE。 Aquaporin-4 (AQP4) 敲除导致更大的血肿体积和更严重的血脑屏障破坏。此外，在野生型组中，多种连接蛋白43 (Cx43)抑制剂减少了血肿体积和血脑屏障破坏，但在AQP4敲除组中则没有。综上所述，优化的HE模型采用高血压、高血糖诱导，以血肿体积扩大≥45.0%为标准。 HH-HE 会导致 BBB 破坏，这取决于 AQP4 和 Cx43。