Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption.
Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption.
复制标题
一氧化碳释放分子 3 通过抑制神经炎症和减轻血脑屏障破坏来预防缺血性中风
DOI：
10.1186/s12974-018-1226-1
复制
发表时间：
2018-06-21
影响因子：
9.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Wang J;Zhang D;Fu X;Yu L;Lu Z;Gao Y;Liu X;Man J;Li S;Li N;Chen X;Hong M;Yang Q;Wang J
在低水平下，一氧化碳（CO）已被证明通过其潜在的抗炎、抗凋亡和抗增殖特性对多个器官和组织有有益的影响。然而，水溶性CORM释放分子(CORM)-3在缺血性脑卒中中的作用及其机制尚不清楚。方法观察CORM-3在小鼠短暂性大脑中动脉闭塞（tMCAO）模型中的作用。在tMCAO后1小时再灌注时或假手术后1小时通过眶后注射CORM-3或生理盐水。我们在缺血后24和72小时评估梗死体积和脑含水量，缺血后6和72小时评估血脑屏障通透性，并在第1、3、7和14天评估神经功能缺损。结果经tMCAO处理的小鼠中，与盐水处理的小鼠相比，经CORM-3处理的小鼠梗死面积明显减小，神经元核抗原（NeuN）和微管相关蛋白2的表达明显增加。与对照组相比，corm -3处理的小鼠梗死周围区活化的小胶质细胞明显减少，并且离子钙结合适配器分子(Iba)-1、肿瘤坏死因子-α和白细胞介素1β的表达下调。在tmcao后的第3、7和14天，corm -3处理的小鼠脑含水量显著降低，神经功能改善。最后，CORM-3处理减少了埃文斯蓝渗漏；血小板源性生长因子受体-β、紧密连接蛋白ZO-1和基质蛋白层粘连蛋白的表达增加；降低基质金属蛋白酶-9蛋白水平。结论再灌注时给予corm -3治疗可通过抑制神经炎症和减轻血脑屏障破坏来减轻缺血再灌注性脑损伤。我们的数据表明，CORM-3可能为缺血性脑卒中提供有效的治疗。
BackgroundAt low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear.MethodsWe investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO). CORM-3 or saline was administered to mice by retro-orbital injection at the time of reperfusion after 1-h tMCAO or at 1 h after sham surgery. We assessed infarct volume and brain water content at 24 and 72 h after ischemia, blood-brain barrier permeability at 6 and 72 h after ischemia, and neurologic deficits on days 1, 3, 7, and 14.ResultsAmong mice that underwent tMCAO, those that received CORM-3 had significantly smaller infarct volume and greater expression of neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 than did saline-treated mice. CORM-3-treated mice had significantly fewer activated microglia in the peri-infarction zone than did control mice and exhibited downregulated expression of ionized calcium-binding adapter molecule (Iba)-1, tumor necrosis factor-α, and interleukin 1β. CORM-3-treated mice had significantly lower brain water content and enhanced neurologic outcomes on days 3, 7, and 14 post-tMCAO. Lastly, CORM-3 treatment reduced Evans blue leakage; increased expression of platelet-derived growth factor receptor-β, tight junction protein ZO-1, and matrix protein laminin; and decreased protein level of matrix metalloproteinase-9.ConclusionCORM-3 treatment at the time of reperfusion reduces ischemia-reperfusion-induced brain injury by suppressing neuroinflammation and alleviating blood-brain barrier disruption. Our data suggest that CORM-3 may provide an effective therapy for ischemic stroke.
登录
查看更多内容
影响因子：
6.1
作者：
Li Q;Han X;Lan X;Hong X;Li Q;Gao Y;Luo T;Yang Q;Koehler RC;Zhai Y;Zhou J;Wang J
通讯作者：
Wang J
影响因子：
29.7
作者：
Nayak D;Roth TL;McGavern DB
通讯作者：
McGavern DB
影响因子：
6.3
作者：
Li, Qian;Wan, Jieru;Wang, Jian
通讯作者：
Wang, Jian
影响因子：
7.2
作者：
Ginhoux, Florent;Prinz, Marco
通讯作者：
Prinz, Marco
影响因子：
7.4
作者：
Cheng T;Wang W;Li Q;Han X;Xing J;Qi C;Lan X;Wan J;Potts A;Guan F;Wang J
通讯作者：
Wang J