Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors
Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors
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DOI：
10.1161/strokeaha.117.020028
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发表时间：
2018-03-01
期刊：
影响因子：
8.3
通讯作者：
Terpolilli, Nicole A.
中科院分区：
文献类型：
--
作者：
Liu, Hanhan;Dienel, Ari;Terpolilli, Nicole A.
背景和目的：脑微循环紊乱（如微血管痉挛）和神经血管沟通减少决定了蛛网膜下腔出血（SAH）的预后。ET-1（内皮素-1）及其受体与SAH后大动脉痉挛的病理生理学有关;然而，它们在微血管功能障碍发展中的作用目前尚不清楚。在这里，我们研究是否抑制ETA（内皮素A）受体可以减少微血管痉挛后，实验诱导SAH. Methods-SAH在雄性C57 BL/6小鼠大脑中动脉的细丝穿孔。SAH后3小时，制备颅窗，并在ETA受体抑制剂clazosentan给药前、给药期间和给药后，使用双光子显微镜在体内测量软脑膜和脑实质微循环。在单独的实验中，在SAH.Results-Clazosentan治疗对SAH诱导的脑微血管痉挛的数量或严重程度没有影响，也没有影响神经学结局。结论-我们的结果表明，在SAH后介导大动脉痉挛的ETA受体似乎在微动脉痉挛的发展中不起作用，这表明出血后痉挛是由脑大血管和脑小血管中不同的机制介导的。鉴于脑微血管功能障碍是SAH后预后的关键因素，迫切需要进一步研究出血后微血管痉挛的机制。
Background and Purpose-Perturbations in cerebral microcirculation (eg, microvasospasms) and reduced neurovascular communication determine outcome after subarachnoid hemorrhage (SAH). ET-1 (endothelin-1) and its receptors have been implicated in the pathophysiology of large artery spasms after SAH; however, their role in the development of microvascular dysfunction is currently unknown. Here, we investigated whether inhibiting ETA (endothelin A) receptors can reduce microvasospasms after experimentally induced SAH.Methods-SAH was induced in male C57BL/6 mice by filament perforation of the middle cerebral artery. Three hours after SAH, a cranial window was prepared and the pial and parenchymal cerebral microcirculation was measured in vivo using two-photon microscopy before, during, and after administration of the ETA receptor inhibitor clazosentan. In separate experiments, the effect of clazosentan treatment on neurological outcome was measured 3 days after SAH.Results-Clazosentan treatment had no effect on the number or severity of SAH-induced cerebral microvasospasms nor did it affect neurological outcome.Conclusions-Our results indicate that ETA receptors, which mediate large artery spasms after SAH, do not seem to play a role in the development of microarterial spasms, suggesting that posthemorrhagic spasms are mediated by distinct mechanisms in large and small cerebral vessels. Given that cerebral microvessel dysfunction is a key factor for outcome after SAH, further research into the mechanisms that underlie posthemorrhagic microvasospasms is urgently needed.