Age exacerbates surgery-induced cognitive impairment and neuroinflammation in Sprague-Dawley rats: the role of IL-4
Age exacerbates surgery-induced cognitive impairment and neuroinflammation in Sprague-Dawley rats: the role of IL-4
复制标题
DOI：
10.1016/j.brainres.2017.04.004
复制
发表时间：
2017-06-15
期刊：
影响因子：
2.9
通讯作者：
Cao, Xuezhao
中科院分区：
文献类型：
--
作者：
Li, Zhe;Liu, Fang;Cao, Xuezhao
年龄是术后认知功能障碍发生的最主要危险因素。本研究探讨了抗炎性白细胞介素（IL）-4在手术诱导的认知障碍和神经炎症反应的年龄相关差异中的潜在作用。对成年和老年Sprague-Dawley雄性大鼠进行部分肝切除术或部分肝切除术，并在小脑延髓池输注IL-4。在术后第1、3和7天，对大鼠进行反向Morris水迷宫测试。在每个时间点测量海马IL-1 β、IL-6、IL-4和IL-4受体（IL-4 R）。脑源性神经营养因子（BDNF）、突触素、离子化钙结合衔接分子1（Iba-1）、小胶质细胞M2表型标记物Argl和CD 200也在海马中进行了检查。年龄诱导了术后第1天和第3天由手术应激引发的认知障碍加重和神经炎症反应放大。抗炎细胞因子IL-4和BDNF也在同一时间点在老年大鼠中发现相应的下降。用IL-4治疗下调促炎细胞因子的表达（例如，IL-1 β和IL-6），增加脑中BDNF和突触素的水平，并改善行为表现。在小脑延髓池输注IL-4后还观察到Argl表达增加和高水平的CD 200。与年龄相关的IL-4表达减少加剧了手术诱导的认知缺陷，并夸大了神经炎症反应。用IL-4治疗可能通过增强BDNF和突触素表达、抑制小胶质细胞活化和减少促炎细胞因子的相关产生来减弱这些作用。(C)2017爱思唯尔B. V.保留所有权利。
Age is the most prominent risk factor for the development of postoperative cognitive dysfunction. This study investigated the potential role of anti-inflammatory interleukin (IL)-4 in age-related differences of surgery-induced cognitive deficits and neuroinflammatory responses. Both adult and aged Sprague-Dawley male rats were subjected to partial hepatectomy or partial hepatectomy with a cisterna magna infusion of IL-4. On postoperative days 1, 3, and 7, the rats were subjected to a reversed Morris water maze test. Hippocampal IL-1 beta, IL-6, IL-4, and IL-4 receptor (IL-4R) were measured at each time point. Brain derived neurotrophic factor (BDNF), synaptophysin, Ionized calcium-binding adapter molecule 1 (lba-1), microglial M2 phenotype marker Argl, and CD200 were also examined in the hippocampus. Age induced an exacerbated cognitive impairment and an amplified neuroinflammatory response triggered by surgical stress on postoperative days 1 and 3. A corresponding decline in the anti-inflammatory cytokine IL-4 and BDNF were also found in the aged rats at the same time point. Treatment with IL-4 downregulated the expression of proinflammatory cytokines (e.g., IL-1 beta and IL-6), increased the levels of BDNF and synaptophysin in the brain and improved the behavioral performance. An increased Argl expression and a high level of CD200 were also observed after a cisterna magna infusion of IL-4. An age-related decrease in IL-4 expression exacerbated surgery-induced cognitive deficits and exaggerated the neuroinflammatory responses. Treatment with IL-4 potentially attenuated these effects by enhancing BDNF and synaptophysin expression, inhibiting microglia activation and decreasing the associated production of proinflammatory cytokines. (C) 2017 Elsevier B.V. All rights reserved.