Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms
Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms
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DOI：
10.1177/0271678x15605848
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发表时间：
2016-12-01
影响因子：
6.3
通讯作者：
Plesnila, Nikolaus
中科院分区：
文献类型：
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作者：
Terpolilli, Nicole A.;Feiler, Sergej;Plesnila, Nikolaus
蛛网膜下腔出血是一种预后特别差的卒中亚型。最近的研究结果表明，出血后早期发生的软脑膜小动脉收缩可能是导致脑缺血和蛛网膜下腔出血后不良结局的原因。由于我们最近假设一氧化氮的缺乏可能会导致出血后微血管痉挛，我们的目的是研究吸入一氧化氮，选择性地提供一氧化氮缺血微血管的治疗范例，是否能够扩张出血后微血管痉挛，从而改善实验性蛛网膜下腔出血后的结果。对C57 BL/6小鼠进行实验性SAH。蛛网膜下腔出血后3小时，通过活体显微镜定量软脑膜动脉痉挛，然后小鼠接受吸入一氧化氮或载体。为了诱导大动脉痉挛，小鼠接受脑池内注射自体血。吸入一氧化氮可显著减少蛛网膜下腔出血引起的出血后微血管痉挛的数量和严重程度，而对大动脉痉挛的作用有限。这导致较少的脑水肿形成，较少的海马神经元丢失，缺乏死亡率，并显着改善蛛网膜下腔出血后的神经功能结局。这表明软脑膜小动脉痉挛对蛛网膜下腔出血后的结局起主要作用，而一氧化氮缺乏是出血后微血管功能障碍的重要机制。吸入一氧化氮逆转微血管功能障碍可能是蛛网膜下腔出血的一种有前途的治疗策略。
Subarachnoid hemorrhage is a stroke subtype with particularly bad outcome. Recent findings suggest that constrictions of pial arterioles occurring early after hemorrhage may be responsible for cerebral ischemia and - subsequently unfavorable outcome after subarachnoid hemorrhage. Since we recently hypothesized that the lack of nitric oxide may cause post-hemorrhagic microvasospasms, our aim was to investigate whether inhaled nitric oxide, a treatment paradigm selectively delivering nitric oxide to ischemic microvessels, is able to dilate post-hemorrhagic microvasospasms; thereby improving outcome after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to experimental SAH. Three hours after subarachnoid hemorrhage pial artery spasms were quantified by intravital microscopy, then mice received inhaled nitric oxide or vehicle. For induction of large artery spasms mice received an intracisternal injection of autologous blood. Inhaled nitric oxide significantly reduced number and severity of subarachnoid hemorrhage-induced post-hemorrhage microvasospasms while only having limited effect on large artery spasms. This resulted in less brain-edema-formation, less hippocampal neuronal loss, lack of mortality, and significantly improved neurological outcome after subarachnoid hemorrhage. This suggests that spasms of pial arterioles play a major role for the outcome after subarachnoid hemorrhage and that lack of nitric oxide is an important mechanism of post-hemorrhagic microvascular dysfunction. Reversing microvascular dysfunction by inhaled nitric oxide might be a promising treatment strategy for subarachnoid hemorrhage.