Isoflurane Conditioning Provides Protection against Subarachnoid Hemorrhage Induced Delayed Cerebral Ischemia through NF-kB Inhibition.
Isoflurane Conditioning Provides Protection against Subarachnoid Hemorrhage Induced Delayed Cerebral Ischemia through NF-kB Inhibition.
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异氟烷调节可通过NF-KB抑制作用，可防止蛛网膜下腔出血引起的延迟脑缺血。
DOI：
10.3390/biomedicines11041163
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发表时间：
2023-04-12
期刊：
影响因子：
4.7
通讯作者：
Athiraman, Umeshkumar
中科院分区：
文献类型：
--
作者：
Liu, Meizi;Jayaraman, Keshav;Mehla, Jogender;Diwan, Deepti;Nelson, James W. W.;Hussein, Ahmed E. E.;Vellimana, Ananth K. K.;Abu-Amer, Yousef;Zipfel, Gregory J. J.;Athiraman, Umeshkumar
迟发性脑缺血（DCI）是继动脉瘤性蛛网膜下腔出血（SAH）之后导致预后不良的最大可治疗原因。活化 B 细胞的核因子 Kappa 轻链增强子 (NF-kB) 是一种已知作为炎症关键介质的转录因子，在 SAH 中表达上调，并且在病理上与血管痉挛相关。我们之前表明，短暂接触异氟烷（一种吸入麻醉剂）可以在 SAH 后提供多方面的 DCI 保护。我们当前研究的目的是探讨 NF-kB 在异氟烷调节诱导的神经血管保护中对 SAH 诱导的 DCI 的作用。将 12 周龄野生型雄性小鼠 (C57BL/6) 分为五组：假手术组、SAH 组、SAH + 吡咯烷二硫代氨基甲酸酯组（PDTC，一种选择性 NF-kB 抑制剂）、SAH + 异氟烷调理组、SAH + PDTC 异氟烷调理组。实验性 SAH 通过血管内穿孔进行。用2%异氟烷进行麻醉调理1小时，SAH后1小时。腹腔注射三剂PDTC（100 mg/kg）。通过免疫荧光染色评估 SAH 后 NF-kB 和小胶质细胞的激活以及 NF-kB 的细胞来源。评估血管痉挛、微血管血栓形成和神经评分。 SAH后NF-kB被激活；它通过异氟烷调节而减弱。小胶质细胞被激活并被发现是 SAH 后 NF-kB 表达的主要来源。异氟烷调理可减弱 SAH 后小胶质细胞的活化和小胶质细胞中 NF-kB 的表达。异氟烷调理和 PDTC 分别减轻大动脉血管痉挛和微血管血栓形成，从而改善 SAH 后的神经功能缺损。在 PDTC 组中添加异氟烷并没有提供任何额外的 DCI 保护。这些数据表明 SAH 后异氟烷调节诱导的 DCI 保护至少部分是通过下调 NF-kB 通路介导的。
Delayed cerebral ischemia (DCI) is the largest treatable cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-kB), a transcription factor known to function as a pivotal mediator of inflammation, is upregulated in SAH and is pathologically associated with vasospasm. We previously showed that a brief exposure to isoflurane, an inhalational anesthetic, provided multifaceted protection against DCI after SAH. The aim of our current study is to investigate the role of NF-kB in isoflurane-conditioning-induced neurovascular protection against SAH-induced DCI. Twelve-week-old wild type male mice (C57BL/6) were divided into five groups: sham, SAH, SAH + Pyrrolidine dithiocarbamate (PDTC, a selective NF-kB inhibitor), SAH + isoflurane conditioning, and SAH + PDTC with isoflurane conditioning. Experimental SAH was performed via endovascular perforation. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. Three doses of PDTC (100 mg/kg) were injected intraperitoneally. NF-kB and microglial activation and the cellular source of NF-kB after SAH were assessed by immunofluorescence staining. Vasospasm, microvessel thrombosis, and neuroscore were assessed. NF-kB was activated after SAH; it was attenuated by isoflurane conditioning. Microglia was activated and found to be a major source of NF-kB expression after SAH. Isoflurane conditioning attenuated microglial activation and NF-kB expression in microglia after SAH. Isoflurane conditioning and PDTC individually attenuated large artery vasospasm and microvessel thrombosis, leading to improved neurological deficits after SAH. The addition of isoflurane to the PDTC group did not provide any additional DCI protection. These data indicate isoflurane-conditioning-induced DCI protection after SAH is mediated, at least in part, via downregulating the NF-kB pathway.
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影响因子：
3.7
作者：
You WC;Wang CX;Pan YX;Zhang X;Zhou XM;Zhang XS;Shi JX;Zhou ML
通讯作者：
Zhou ML
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
DOI：
10.18632/aging.202349
发表时间：
2020-12-28
期刊：
Aging
影响因子：
--
作者：
Yao Z;Liu N;Zhu X;Wang L;Zhao Y;Liu Q;Gao C;Li J
通讯作者：
Li J
影响因子：
15.9
作者：
Tak, PP;Firestein, GS
通讯作者：
Firestein, GS
影响因子：
--
作者：
Vlasov, T D;Korzhevskii, D E;Polyakova, E A
通讯作者：
Polyakova, E A