Selective histamine H2 receptor agonists alleviate blood-brain barrier disruption by promoting the expression of vascular protective factors following traumatic brain injury in mice
Selective histamine H2 receptor agonists alleviate blood-brain barrier disruption by promoting the expression of vascular protective factors following traumatic brain injury in mice
复制标题
选择性组胺 H2 受体激动剂通过促进小鼠脑外伤后血管保护因子的表达来减轻血脑屏障破坏
DOI：
10.1016/j.jphs.2022.08.003
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发表时间：
2022
影响因子：
3.5
通讯作者：
Hiroyuki Mizuguchi
中科院分区：
文献类型：
--
作者：
Shotaro Michinaga;Kiyomi Sonoda;Naoki Inazuki;Manae Ezaki;Hiroki Awane;Kahori Shimizu;Shigeru Hishinuma;Hiroyuki Mizuguchi
组胺是一种主要的神经递质，可通过 H2 受体减轻缺血性损伤后的神经元损伤。在此，我们研究了 H2 受体激动剂对创伤性脑损伤 (TBI) 后血脑屏障 (BBB) 破坏的影响。雄性 ddY 小鼠用于生成 TBI 模型，其中液压冲击诱导流体冲击损伤 (FPI)。使用伊文思蓝外渗评估血脑屏障破坏。 FPI 后 3 小时至 3 天将 H2 受体激动剂安他明和二马普利注射到侧脑室 (i.c.v.) 或尾静脉 (i.v.)。 i.c.v.或静脉注射给予 amthamine 和 dimaprit 可减少 FPI 诱导的伊文思蓝外渗，并促进血管保护因子（包括 angiopoietin-1 和 sonic hedgehog）的 mRNA 表达。联合使用 H2 受体拮抗剂雷尼替丁可抑制这些作用。在受损皮层的星形胶质细胞和脑微血管内皮细胞 (BMEC) 中观察到 H2 受体的表达。 Amthamine 和 dimaprit 治疗可促进星形胶质细胞和 BMEC 中血管保护因子的 mRNA 表达。这些结果表明，H2 受体激动剂通过增加星形胶质细胞和 BMEC 中血管保护因子的表达来减轻 TBI 诱导的 BBB 破坏。
Histamine is a major neurotransmitter and alleviates neuronal damage after ischemic injury via H2receptors. Herein, we investigated the effects of H2receptor agonists on the blood-brain barrier (BBB) disruption after traumatic brain injury (TBI). Male ddY mice were used to generate the TBI model, in which a fluid percussion injury (FPI) was induced by a hydraulic impact. The BBB disruption was evaluated using Evans blue extravasation. H2receptor agonists, amthamine and dimaprit, were administered into the lateral cerebroventricle (i.c.v.) or tail vein (i.v.) from 3 hours to 3 days after FPI. The i.c.v. or i.v. administration of amthamine and dimaprit reduced FPI-induced Evans blue extravasation and promoted mRNA expression of vascular protective factors, including angiopoietin-1 and sonic hedgehog. The co-administration of ranitidine, a H2receptor antagonist, inhibited these effects. Expression of the H2receptor was observed in astrocytes and brain microvascular endothelial cells (BMECs) in the injured cortex. Treatment with amthamine and dimaprit promoted mRNA expression of vascular protective factors in astrocytes and BMECs. These results suggest that H2receptor agonists alleviate TBI-induced BBB disruption by increasing the expression of vascular protective factors in astrocytes and BMECs.