Inflammatory cytokines are involved in dihydrocapsaicin (DHC) and regional cooling infusion (RCI)-induced neuroprotection in ischemic rat
Inflammatory cytokines are involved in dihydrocapsaicin (DHC) and regional cooling infusion (RCI)-induced neuroprotection in ischemic rat
复制标题
炎症细胞因子参与二氢辣椒素（DHC）和局部冷却输注（RCI）诱导的缺血大鼠神经保护
DOI：
10.1016/j.brainres.2018.12.033
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发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Ji, Xunming
中科院分区：
文献类型：
--
作者：
Wu, Di;Zhi, Xinglong;Ji, Xunming
目的：药理学低温-二氢辣椒素（DHC）和动脉内区域冷却输注（RCI）的组合被发现增强低温的效率和低温诱导的急性缺血性中风中的神经保护的功效。本研究的目的是探讨联合用药是否能诱导长期的神经保护作用，以及可能的机制。方法：采用中空纤维线栓法造成大鼠大脑中动脉闭塞（MCAO）2 h。将缺血大鼠随机分组，通过腹膜内（i. p.）注射DHC、通过RCI的6 ml冷盐水（4 ℃）的物理低温、组合和不处理。在21天的时间里，通过MRI的梗死体积和网格行走和平衡木平衡测试的神经功能缺损来确定脑损伤。以伊文思蓝（EB）含量测定血脑屏障（BBB）。结果：DHC与RCI联用可明显缩小脑梗死体积，减少脑梗死后神经功能缺损（P < 0.05）。由于联合治疗，血脑屏障渗漏和促炎细胞因子（IFN-γ、IL-2和TNF-α）显著降低（p < 0.05），而保护性细胞因子（IL-4和IL-10）在梗死周围区域增加（p < 0.05）。我们的研究结果提供了一个提示，将组合方法从实验室翻译到床边。
Objective: The combination of pharmacological hypothermia - dihydrocapsaicin (DHC) and intra-arterial regional cooling infusions (RCI) was found to enhance the efficiency of hypothermia and efficacy of hypothermia induced neuroprotection in acute ischemic stroke. The aim of this study was to explore whether the combination could induce a long-term neuroprotective effects, as well as the underlying mechanism.Methods: Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2h using intraluminal hollow filament. The ischemic rats were randomized to receive pharmacological hypothermia by intraperitoneal (i.p.) injection of DHC, physical hypothermia by RCI of 6 ml cold saline (4 degrees C), the combination, and no treatment. Over a 21-day period, brain damage was determined by infarct volume with MRI, and neurological deficit with grid-walking and beam balance tests. Blood brain barrier (BBB) was assessed by Evans-Blue (EB) contents. Inflammatory cytokines were determined in peri-infarct area by antibody array and ELISA.Results: The combination of DHC and RCI reduced (p < 0.05) infarct volume and neurologic deficit after stroke. BBB leakage and pro-inflammatory cytokines (IFN-gamma, IL-2, and TNF-alpha) were significantly decreased (p < 0.05) because of the combination, while protective cytokines (IL-4 and IL-10) were increased (p < 0.05) in the peri-infarct area.Conclusions: The combination approach enhanced the efficacy of hypothermia-induced neuroprotection following ischemic stroke. Our findings provide a hint to translate the combination method from bench to bedside.