Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, Henan, China.
J Neuroinflammation. 2018 Jun 21;15(1):188. doi: 10.1186/s12974-018-1226-1.
At 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.
We 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.
Among 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.
CORM-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.
一氧化碳（CO）在低水平时已被证明通过其潜在的抗炎、抗凋亡和抗增殖特性对多种器官和组织具有有益作用。然而，一氧化碳释放分子（CORM）-3，一种水溶性 CORM，对缺血性中风的影响及其作用机制尚不清楚。
我们研究了 CORM-3 在短暂性大脑中动脉闭塞（tMCAO）小鼠模型中的作用。在 1 小时 tMCAO 再灌注时或假手术后 1 小时通过眼眶后注射向小鼠给予 CORM-3 或生理盐水。我们在缺血后 24 小时和 72 小时评估梗死体积和脑水含量，在缺血后 6 小时和 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。
在接受 tMCAO 的小鼠中，接受 CORM-3 治疗的小鼠的梗死体积明显小于生理盐水治疗的小鼠，神经元核抗原（NeuN）和微管相关蛋白 2 的表达也明显更高。CORM-3 治疗的小鼠在梗死周围区的活化小胶质细胞明显少于对照组小鼠，并表现出下调的离子钙结合接头分子（Iba）-1、肿瘤坏死因子-α和白细胞介素 1β的表达。CORM-3 治疗的小鼠在 tMCAO 后第 3、7 和 14 天的脑水含量明显更低，神经功能结果也更好。最后，CORM-3 治疗减少了 Evans 蓝漏出；增加了血小板衍生生长因子受体-β、紧密连接蛋白 ZO-1 和基质蛋白层粘连蛋白的表达；并降低了基质金属蛋白酶-9 的蛋白水平。
再灌注时给予 CORM-3 治疗通过抑制神经炎症和减轻血脑屏障破坏来减少缺血再灌注引起的脑损伤。我们的数据表明，CORM-3 可能为缺血性中风提供一种有效的治疗方法。
