The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage
The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage
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DOI：
10.1007/s12975-018-0685-0
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发表时间：
2019-12-01
影响因子：
6.9
通讯作者：
Ohkuma, Hiroki
中科院分区：
文献类型：
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作者：
Fumoto, Toshio;Naraoka, Masato;Ohkuma, Hiroki
氧化应激在蛛网膜下腔出血（SAH）后早期脑损伤（EBI）的多种发病机制中起着至关重要的作用。微循环功能障碍被认为是EBI的重要病理基础。然而，除了血脑屏障（BBB）的破坏，氧化应激对微血管的影响仍有待阐明。本研究的目的是探讨氧化应激对EBI微循环完整性的作用。使用血管内穿孔技术在雄性Sprague-Dawley大鼠中诱导SAH。自由基清除剂依达拉奉通过腹腔注射给药。在SAH诱导后24 h测定SAH分级、神经功能评分、脑含水量和BBB通透性。此外，分析SAH后24小时采集的皮质样本，以探讨氧化应激、微血管壁细胞凋亡、微痉挛和微血栓形成。依达拉奉治疗显著改善神经功能缺损、脑水肿和BBB破坏。此外，SAH诱导后，氧化应激诱导的微血管内皮细胞和周细胞的修饰和随后的凋亡增加，而依达拉奉的给药抑制了这一点。与凋亡细胞抑制一致，依达拉奉给药也抑制了微血栓形成。氧化应激在EBI微血管的多种病理变化中起着关键作用。抗氧化剂是治疗SAH后微血管障碍的潜在候选药物。
Oxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique. A free radical scavenger, edaravone, was administered prophylactically by intraperitoneal injection. SAH grade, neurological score, brain water content, and BBB permeability were measured at 24 h after SAH induction. In addition, cortical samples taken at 24 h after SAH were analyzed to explore oxidative stress, microvascular mural cell apoptosis, microspasm, and microthrombosis. Edaravone treatment significantly ameliorated neurological deficits, brain edema, and BBB disruption. In addition, oxidative stress-induced modifications and subsequent apoptosis of microvascular endothelial cells and pericytes increased after SAH induction, while the administration of edaravone suppressed this. Consistent with apoptotic cell inhibition, microthromboses were also inhibited by edaravone administration. Oxidative stress plays a pivotal role in the induction of multiple pathological changes in microvessels in EBI. Antioxidants are potential candidates for the treatment of microvascular disturbances after SAH.