Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice.
Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice.
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DOI：
10.1016/j.nbd.2016.09.013
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发表时间：
2016-12
影响因子：
6.1
通讯作者：
Yu, Shan Ping
中科院分区：
文献类型：
--
作者：
Lee, Jin Hwan;Wei, Zheng Z.;Cao, Wenyuan;Won, Soonmi;Gu, Xiaohuan;Winter, Megan;Dix, Thomas A.;Wei, Ling;Yu, Shan Ping
关键词：
中风是美国和全球人类生命和健康的主要威胁，而中风患者的有效治疗方法却很少。临床前和临床研究表明，低温治疗（TH）是治疗中风的潜在方法。使用新型神经降压素受体 1 (NTR1) 激动剂，我们在啮齿动物模型中证明了药物诱导的低温和对缺血性中风、出血性中风和创伤性脑损伤 (TBI) 后脑损伤的保护作用。为了进一步表征 TH 诱导的脑保护机制，我们研究了 NTR1 激动剂 HPI-201 或物理（冰/冷空气）诱导的 TH（±33°C 6 小时）对小鼠缺血性中风和皮质神经元培养中氧糖剥夺（OGD）后炎症反应的影响。局灶性皮质缺血 7 天后，半暗带中的小胶质细胞激活达到峰值水平，中风后 30 分钟开始 TH 治疗可显着减弱这种激活。 RT-PCR 和 Western blot 分析显示，TH 治疗降低了 M1 型反应因子的表达，包括肿瘤坏死因子-α (TNF-α)、白介素-1β (IL-1β)、IL-12、IL-23 和诱导型一氧化氮合酶 (iNOS)。同时，TH 处理增加了 M2 型反应因子的表达，包括 IL-10、Fizz1、Ym1 和精氨酸酶-1。在缺血大脑和进行 OGD 的皮质神经元/BV2 小胶质细胞培养物中，TH 减弱了单核细胞趋化蛋白 1 (MCP-1) 和巨噬细胞炎症蛋白 1α (MIP-1α) 的表达，这两种趋化因子是调节小胶质细胞活化和浸润的两个关键趋化因子。一致的是，OGD 期间的物理冷却在 OGD 后 16 小时显着减少了小胶质细胞的迁移。最后，TH 改善了中风后 1、3 和 7 天的功能恢复。这项研究揭示了低温介导对炎症因子表达、小胶质细胞极化、迁移的调节的第一个证据，并表明抗炎作用是 TH 疗法脑保护作用的重要机制。
Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models. To further characterize the mechanism of TH-induced brain protection, we examined the effect of TH (at ±33°C for 6 hrs) induced by the NTR1 agonist HPI-201 or physical (ice/cold air) cooling on inflammatory responses after ischemic stroke in mice and oxygen glucose deprivation (OGD) in cortical neuronal cultures. Seven days after focal cortical ischemia, microglia activation in the penumbra reached a peak level, which was significantly attenuated by TH treatments commenced 30 min after stroke. The TH treatment decreased the expression of M1 type reactive factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12, IL-23, and inducible nitric oxide synthase (iNOS) measured by RT-PCR and Western blot analyses. Meanwhile, TH treatments increased the expression of M2 type reactive factors including IL-10, Fizz1, Ym1, and arginase-1. In the ischemic brain and in cortical neuronal/BV2 microglia cultures subjected to OGD, TH attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α), two key chemokines in the regulation of microglia activation and infiltration. Consistently, physical cooling during OGD significantly decreased microglia migration 16 hrs after OGD. Finally, TH improved functional recovery at 1, 3, and 7 days after stroke. This study reveals the first evidence for hypothermia mediated regulation on inflammatory factor expression, microglia polarization, migration and indicates that the anti-inflammatory effect is an important mechanism underlying the brain protective effects of a TH therapy.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
4.8
作者：
Choi, Ko-Eun;Hall, Casey L.;Yu, Shan P.
通讯作者：
Yu, Shan P.
DOI：
10.1038/jcbfm.2013.52
发表时间：
2013-07
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.6
作者：
Guillemette, A.;Dansereau, M. A.;Sarret, P.
通讯作者：
Sarret, P.
影响因子：
8.8
作者：
Geurts, Marjolein;Macleod, Malcolm R.;van der Worp, H. Bart
通讯作者：
van der Worp, H. Bart