HIF-1α Mediates Isoflurane-Induced Vascular Protection in Subarachnoid Hemorrhage.
HIF-1α Mediates Isoflurane-Induced Vascular Protection in Subarachnoid Hemorrhage.
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DOI：
10.1002/acn3.170
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发表时间：
2015-04
影响因子：
5.3
通讯作者：
Zipfel, Gregory J.
中科院分区：
文献类型：
--
作者：
Milner, Eric;Johnson, Andrew W.;Nelson, James W.;Harries, Michael D.;Gidday, Jeffrey M.;Han, Byung Hee;Zipfel, Gregory J.
动脉瘤性蛛网膜下腔出血（SAH）后的预后严重依赖于延迟性脑缺血（DCI）——这一过程主要由血管事件驱动，包括脑血管痉挛、微血管血栓形成和微血管功能障碍。本研究试图确定后适应对sah诱导的DCI的影响，后适应是一种现象，即随后暴露于轻度应激源可增强对严重损伤的内源性保护。成年雄性C57BL/6小鼠分别接受假手术、SAH或SAH +异氟醚后处理。每天通过感觉运动评分评估神经预后。3天后测量脑血管痉挛、微血管血栓形成和微血管功能障碍对DCI的影响。通过定量聚合酶链反应评估异氟醚诱导的缺氧诱导因子1α (HIF-1α)依赖基因的变化。通过2-甲氧基雌二醇（2ME2）或通过内皮细胞HIF-1α-null小鼠（EC-HIF-1α-null）从药理学角度抑制HIF-1α。所有实验均采用随机盲法进行。异氟醚后处理在SAH后的临床相关时间点启动，可显著减少野生型（WT）小鼠的脑血管痉挛、微血管血栓形成、微血管功能障碍和神经功能障碍。异氟醚调节hif -1α依赖基因的变化，在2me2处理的WT小鼠和ec - hif -1α-无效的小鼠中被消除。异氟醚诱导的DCI保护作用在2me2处理的WT小鼠和ec - hif -1α-缺失小鼠中减弱。异氟醚后处理在SAH中提供了强大的hif -1α介导的大血管和微血管保护，从而改善了神经系统预后。这些结果表明，脑血管是异氟醚后处理提供的脑保护的关键靶点，HIF-1α是这种血管保护的关键介质。他们还发现异氟醚后处理是一种很有前途的治疗SAH的新方法。
Outcome after aneurysmal subarachnoid hemorrhage (SAH) depends critically on delayed cerebral ischemia (DCI) – a process driven primarily by vascular events including cerebral vasospasm, microvessel thrombosis, and microvascular dysfunction. This study sought to determine the impact of postconditioning – the phenomenon whereby endogenous protection against severe injury is enhanced by subsequent exposure to a mild stressor – on SAH-induced DCI. Adult male C57BL/6 mice were subjected to sham, SAH, or SAH plus isoflurane postconditioning. Neurological outcome was assessed daily via sensorimotor scoring. Contributors to DCI including cerebral vasospasm, microvessel thrombosis, and microvascular dysfunction were measured 3 days later. Isoflurane-induced changes in hypoxia-inducible factor 1alpha (HIF-1α)-dependent genes were assessed via quantitative polymerase chain reaction. HIF-1α was inhibited pharmacologically via 2-methoxyestradiol (2ME2) or genetically via endothelial cell HIF-1α-null mice (EC-HIF-1α-null). All experiments were performed in a randomized and blinded fashion. Isoflurane postconditioning initiated at clinically relevant time points after SAH significantly reduced cerebral vasospasm, microvessel thrombosis, microvascular dysfunction, and neurological deficits in wild-type (WT) mice. Isoflurane modulated HIF-1α-dependent genes – changes that were abolished in 2ME2-treated WT mice and EC-HIF-1α-null mice. Isoflurane-induced DCI protection was attenuated in 2ME2-treated WT mice and EC-HIF-1α-null mice. Isoflurane postconditioning provides strong HIF-1α-mediated macro- and microvascular protection in SAH, leading to improved neurological outcome. These results implicate cerebral vessels as a key target for the brain protection afforded by isoflurane postconditioning, and HIF-1α as a critical mediator of this vascular protection. They also identify isoflurane postconditioning as a promising novel therapeutic for SAH.
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高压氧预处理诱导大鼠缺血耐受的机制涉及上调缺氧诱导因子-1α和促红细胞生成素。
影响因子：
3.3
作者：
Gu, Guo-Jun;Li, Yun-Ping;Sun, Xue-Jun
通讯作者：
Sun, Xue-Jun
DOI：
10.1523/jneurosci.4686-08.2008
发表时间：
2008-12-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Han BH;Zhou ML;Abousaleh F;Brendza RP;Dietrich HH;Koenigsknecht-Talboo J;Cirrito JR;Milner E;Holtzman DM;Zipfel GJ
通讯作者：
Zipfel GJ
影响因子：
8.8
作者：
Altay O;Hasegawa Y;Sherchan P;Suzuki H;Khatibi NH;Tang J;Zhang JH
通讯作者：
Zhang JH
影响因子：
2.9
作者：
Li, Qi-fang;Zhu, Ye-sen;Jiang, Hong
通讯作者：
Jiang, Hong
影响因子：
8.3
作者：
Fisher M;Feuerstein G;Howells DW;Hurn PD;Kent TA;Savitz SI;Lo EH;STAIR Group
通讯作者：
STAIR Group