小胶质细胞表面受体在术后认知功能障碍中的研究进展

术后认知功能障碍是围术期常见的神经系统并发症,表现为记忆力、注意力、判断力下降,认知和行为改变,严重影响患者预后,增加社会负担。目前术后认知功能障碍的发病机制尚未明确,小胶质细胞过度激活引发的神经炎症是术后认知功能障碍发病的重要机制之一。麻醉和手术等刺激可通过小胶质细胞表面受体的作用导致小胶质细胞过度激活,引发神经炎症的恶性循环,损伤神经元,引起术后认知功能障碍的发生。小胶质细胞表面受体是导致小胶质细胞过度激活发生的关键因素。本文对小胶质细胞表面受体在术后认知功能障碍中的作用进行综述,以期为术后认知功能障碍的机制研究和防治提供参考。     

远隔缺血预处理对老年小鼠神经认知功能及小胶质细胞和突触后致密蛋白95的影响

目的探讨远隔缺血预处理(RIPre)对老年小鼠神经认知功能及小胶质细胞和突触后致密蛋白95(PSD95)的影响。方法采用异氟醚麻醉+腹腔探查术建立围术期神经认知障碍(PND)模型。15月龄老年雄性C57BL/6小鼠,随机分为四组:对照组(C组)、缺血预处理组(RIPre组)、手术麻醉组(S组)和手术麻醉+缺血预处理组(S+RIPre组)。RIPre组和S+RIPre组于PND模型建立前行远隔缺血-再灌注,小鼠后肢血流阻断5 min后血液复流5 min,共重复缺血-复灌3次。术后第3天行旷场实验,第4、5天分别行条件性恐惧实验训练和测试。每组另外取6只小鼠于术后取海马组织,采用Western blot法检测术后第3天海马离子钙结合适配器分子1(Iba1)和PSD95蛋白含量,ELISA法检测术后第3天海马IL-6浓度。结果与C组比较,S组中央区域停留时间明显减少,僵直反应百分比明显降低,术后第3天海马IL-6浓度明显升高,PSD95蛋白含量明显降低,Iba1蛋白含量明显升高(P0.05)。与S组比较,S+RIPre组中央区域停留时间明显延长,僵直反应百分比明显增加,术后第3天海马IL-6浓度明显降低,PSD95蛋白含量明显升高,Iba1蛋白含量明显降低(P0.05)。结论 RIPre可减轻异氟醚麻醉手术诱发的老龄小鼠神经认知功能障碍,其作用机制可能是RIPre抑制小胶质细胞过度激活,从而减轻对突触可塑性的损伤,并减弱海马神经炎症反应。     

小胶质细胞参与调控术后认知功能障碍的研究进展

背景 术后认知功能障碍（postoperative cognitive dysfunction, POCD）在老年患者中发生率较高。小胶质细胞是一种中枢神经细胞,在中枢神经系统（central nervous system, CNS）生理和病理过程中均发挥重要作用。越来越多的研究表明,小胶质细胞广泛参与神经退行性疾病的发生与发展。 目的 探讨小胶质细胞在POCD中的作用。 内容 简述小胶质细胞对学习记忆的调控作用及其与POCD的相关性。 趋向 小胶质细胞在POCD中的具体作用尚未阐明,继续对此进行深入探究可能为预防和治疗POCD提供新的思路。     

星型胶质细胞和小胶质细胞在1型糖尿病小鼠外周神经病变中的作用

目的 观察星形胶质细胞和小胶质细胞标志物在1型糖尿病外周神经病变小鼠脊髓中的表达变化。
方法 SPF级健康雄性C57BL/6小鼠30只,6周龄,体重18~22 g,采用随机数字表法分为两组：对照组（C组）和糖尿病组（DM组）。DM组采用链脲佐菌素（STZ）（100 mg/kg,连续2 d腹腔注射）制备1型糖尿病小鼠模型,C组给予同等剂量柠檬酸钠缓冲液连续2 d。记录两组小鼠造模前、造模后1、2、4、6、8、10周的体重、随机血糖、机械缩足反应阈（MWT）、热缩足潜伏期（TWL）。生化检测分别选取C组和DM组1周、10周的脊髓。采用Western blot法测定L4—L6脊髓脂肪酸结合蛋白7（FABP7）、星形胶质细胞特异性标记物胶质纤维酸性蛋白（GFAP）、小胶质细胞标记物（CD11b、iba1）表达量,Elisa法测定小鼠脊髓组织中肿瘤坏死因子α（TNF-α）、IL-10浓度,免疫组化法测定足底表皮神经纤维密度（IENFD）。
结果 与C组比较,DM组造模后2、4、6、8、10周体重、MWT明显降低（P＜0.05或P＜0.01）,造模后1、2、4、6、8、10周血糖明显升高（P＜0.01）,造模后4、6、8、10周TWL明显延长（P＜0.05或P＜0.01）;造模后1周FABP7和GFAP表达量明显升高（P＜0.05）;造模后10周FABP7、CD11b、iba1表达量明显升高（P＜0.05）;造模后10周脊髓组织中IL-10、TNF-α浓度明显升高（P＜0.05）;造模后10周IENFD明显降低（P＜0.05）。
结论 糖尿病模型小鼠造模后1周脊髓中星形胶质细胞活化但小胶质细胞无明显改变,而造模后10周星形胶质细胞已恢复正常但小胶质细胞活化,1型糖尿病外周神经病变中星型胶质细胞较小胶质细胞更早的激活。     

Toll样受体4在小胶质细胞炎症反应中的作用与认知功能的关系

概述 小胶质细胞在术后早期中枢炎症反应中担当主角.而Toll样受体4(toll-like receptor 4,TLR4)在小胶质细胞的活化与炎症反应中发挥着不可或缺的作用.中枢炎症细胞因子可通过多种途径影响中枢有关受体或递质功能,从而影响学习记忆和认知能力. 目的 探讨TLR4在小胶质细胞炎症反应中作用及与认知功能的关系. 内容 主要从4个方面进行综述:TLR4与小胶质细胞的关系、小胶质细胞与中枢炎症的关系、炎症和TLR4对认知的影响. 趋向 小胶质细胞在中枢神经系统(central nervous system,CNS)的炎症反应中担当主角.TLR4在小胶质细胞的激活中起关键作用,但TLR4在小胶质细胞相关的中枢炎症反应和认知中的作用尚不清楚.     

Tau蛋白与认知功能

Tau蛋白为正常的生理蛋白,其高度磷酸化对认知功能有影响.围术期存在多种因素可以通过蛋白激酶和蛋白磷酸酶相对活性失衡引起tau的磷酸化,从而影响术后认知功能.     

Tau蛋白与认知功能

Tau蛋白为正常的生理蛋白，其高度磷酸化对认知功能有影响。围术期存在多种因素可以通过蛋白激酶和蛋白磷酸酶相对活性失衡引起tau的磷酸化，从而影响术后认知功能。     

脊髓小胶质细胞活化在大鼠术后持续性痛中的作用

目的 探讨脊髓小胶质细胞活化在大鼠术后持续性痛中的作用.方法选择鞘内置管成功的雄性SD大鼠72只,体重200～250 g,采用随机数字表法,将其随机分为3组(n=24):假手术组、皮肤肌肉切口牵拉组(SMIR组)和米诺环素组.采用皮肤肌肉切口牵拉法建立大鼠术后持续性痛模型,假手术组和SMIR组于术前30 min和术后1～3 d鞘内注射人工脑脊液20 μl,1次,d;米诺环素组于术前30 min和术后1～3 d鞘内注射米诺环素10 μl,1次/d,并在每次注药后经导管注射人工脑脊液10 μl冲洗导管.于术前1 d及术后3、7、12、22和32 d时测定机械缩足反射阈值(MWT),各时点MWT测定结束后,随机取4只大鼠,测定脊髓背角小胶质细胞特异性标记物Iba-1的表达和计数小胶质细胞.结果 与假手术组比较,SMIR组和米诺环素组术后3～22 d时MWT降低,术后3、7 d时脊髓背角Iba-1表达和小胶质细胞计数升高(P＜0.05);与SMIR组比较,米诺环素组术后3～22 d时MWT升高,术后3、7 d时脊髓背角Iba-1表达和小胶质细胞计数降低(P＜0.05).结论 脊髓小胶质细胞的活化参与了大鼠术后持续性痛的形成.

Abstract：

Objective To investigate the role of microglial activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) .Methods Seventy-two male SD rats weighing 200-250 g in which intrathecal (IT) catheter was successfully inserted were randomly divided into 3 groups ( n = 24 each) : group sham operation; group SMIR and group SMIR + FT minocycline (a specific microglia inhibitor) . The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters. Pain behavior was assessed by paw mechanical withdrawal threshold ( MWT) to von Frey filament stimulation at 1 day before (T0,baseline) and 3, 7, 12, 22 and 32 days after operation (T1-5,) . Four animals were sacrificed at each time point in each group for detection of the expression of Iba-1 (a specific marker of microglia) in the spinal dorsal horn by immunofluorescence and the microglia was counted. Results MWT was significantly decreasedat T1-4, while the expression of Iba-1 and microglia counts in the spinal dorsal horn were significantly increased at T1, 2 by SMIR in group Ⅱ. IT minocycline significantly attenuated the hyperalgesia induced by SMIR at T1-4 and decreased Iba-1 expression and microglia counts at T1,2 in group Ⅲ. Conclusion Microglial activation in the spinal cord plays an important role in the development and maintenance of SMIR-evoked persistent postoperative pain in rats.     

手术创伤对不同月龄大鼠认知功能及海马小胶质细胞活化的影响

目的 评价手术创伤对不同月龄大鼠认知功能和海马小胶质细胞活化的影响.方法 健康雄性SD大鼠72只,3～4月龄,采用随机数字表法,将其分为2组:成年对照组(n=30)和成年手术组(n=42).健康雄性SD大鼠72只,18 ～ 20月龄,采用随机数字表法,将其分为2组:老年对照组(n=30)和老年手术组(n=42).手术组腹腔注射5%水合氯醛4～6 ml/kg麻醉下行剖腹探查术,对照组腹腔注射生理盐水1 ml/kg.于术后1～7d开始行水迷宫实验,术后1d采用条件恐怖适应实验检测大鼠术后空间和恐怖记忆能力,术后第1、3、7天时处死大鼠,取海马,采用免疫组化法检测小胶质细胞OX42表达.结果 与成年对照组比较,成年手术组大鼠僵直时间占总时间百分比降低,术后第1天海马小胶质细胞OX42表达上调(P＜0.05),逃避潜伏期及穿过原平台次数差异无统计学意义(P＞0.05);与老年对照组比较,老年手术组大鼠逃避潜伏期延长,穿过原平台次数减少,僵直时间占总时间百分比降低,术后第1和3天海马小胶质细胞OX42表达上调(P＜0.05).结论 手术创伤可降低成年大鼠恐怖记忆能力,但对空间记忆能力影响不明显;手术创伤可降低老年大鼠空间及恐怖记忆能力,与海马小胶质细胞活化有关.     

Potentially undiagnosed cognitive impairment in patients with peripheral arterial disease: A systematic review of the literature

IntroductionIt is purported that patients with peripheral arterial disease (PAD) may have impaired cognitive function due to concomitant cerebrovascular disease. Such disease may be clinically unrecognized but can impact on a patient's recovery and prognosis. The purpose of this systematic review was to interrogate the body of published evidence on undiagnosed cognitive impairment in PAD patients.MethodsA search strategy encompassing MEDLINE, Scopus, and the Cochrane database was developed to identify peer-reviewed articles examining rates of undiagnosed cognitive impairment in patients with PAD. The following search terms were used: ‘PAD’; ‘PVD’; ‘dementia’; ‘peripheral arterial disease’; ‘peripheral vascular disease’; ‘cognitive impairment'; 'alzheimer's disease’ and ‘cogniti1’. Our primary outcome was the incidence of previously undiagnosed cognitive impairment in patients with PAD.ResultsThe initial search yielded 1492 titles. After removal of duplicates, 961 abstracts were screened to ascertain if they were eligible for inclusion. Abstract review yielded 62 full texts for further evaluation. Eight case–control studies consisting of 1161 patients were included. Analysis of these studies revealed that PAD patients performed significantly worse than controls on a variety of neuropsychological measures.ConclusionOur review indicated that PAD patients are more likely to suffer with undiagnosed cognitive impairment than healthy controls.     

甲基莲心碱对七氟烷麻醉后大鼠认知障碍影响的实验研究

目的:探讨甲基莲心碱对七氟烷麻醉后大鼠认知障碍的影响及其分子机制。方法:选取2018年7月将45只SD大鼠按照随机数字表法分为对照组、模型组和甲基莲心碱组,每组15只。模型组和甲基莲心碱组大鼠七氟烷麻醉3 h后自然苏醒,对照组不做处理。甲基莲心碱组大鼠在麻醉之前给予腹腔注射甲基莲心碱5 mg/kg,对照组和模型组大鼠经...     

A video-game based cognitive training for breast cancer survivors with cognitive impairment: A prospective randomized pilot trial

IntroductionWe investigated whether a web-based cognitive training video game is an effective approach to improve cognitive decline in combination with our standard of care for rehabilitation of breast cancer (BC) patients.Materials and methodsSelf-selected BC patients between 18 and 71 years old complaining of disturbing cognitive impairment were studied. The patients received access to a web-based internet video game and online cognitive assessments (Aquasnap, Cambridge, MyCQ™). The early intervention group (n = 23) had a training program of 6 months of at least three times a week for a minimum of 60 min of game playing per week at home in addition to standard of care rehabilitation. The delayed intervention (n = 23) received standard of care for three months, followed by three months of similar MyCQ training. Outcome measures were the MyCQ (sub)scores and Activity of Daily Life (ADL), mood, subjective cognition and functional cognitive status measured by classic neuropsychological tests.ResultsAt baseline the means for CFQ (a measure of self-reported cognitive failure), anxiety, PSQI and self-reflectiveness were beyond normal range in both groups. CFQ improved significantly better in the intervention group (p = 0.029). Combining the evolution over time in the entire population a significant improvement was seen for overall MyCQ score, level of fear, physical and emotional role limitation, and health change (all p < 0.05), but self-reflectivess deteriorated (p < 0.05)). Significant differences in the various MyCQ subtests over time were: improved speed in choice reaction time, visual memory recognition, N back 1 and 2, coding, trail making test B, improved accuracy of N back 1 and 2 (all p < 0.05).ConclusionA program of cognitive training improves cognitive functioning over time. “Aquasnap” has a beneficial effect on the perception of subjective cognitive functioning (CFQ) but the exact role of video gaming in this process remains uncertain.     

紫杉醇诱发神经病理性疼痛和认知功能损伤的相关机制

紫杉醇作为一线化疗用药,其诱发的神经病理性疼痛和认知功能损伤逐渐受到人们的关注。文章结合紫杉醇的药理特性、作用特点,总结近年来紫杉醇对中枢神经元γ-氨基丁酸B型（gamma aminobutyric acid B, GABA B）受体和内质网应激的研究进展,探寻紫杉醇诱发神经病理性疼痛、神经元凋亡、损伤中枢认...     

衰老大脑小胶质细胞异常激活与中枢性炎症研究进展

背景 中枢性炎症反应在老年术后认知功能障碍(post operative cognitive dysfunction,POCD)、阿尔茨海默病(Alzheimer's disease,AD)、帕金森病(Parkinson's disease,PD)等慢性神经退行性疾病的发生发展中至关重要,其具体机制尚不明确.目的 阐明衰老大脑小胶质细胞活性改变及其异常激活对中枢炎症反应的加剧作用.内容 对衰老大脑小胶质细胞异常激活及其可能机制进行阐述.趋向 如何抑制衰老大脑小胶质细胞免疫通路的异常激活是今后的研究方向.     

脊髓小神经胶质细胞在糖尿病痛性周围神经病变中的作用

目的 观察糖尿病痛性周围神经病变大鼠脊髓小神经胶质细胞的变化及腹腔注射丙戊茶碱(propentofylline,PPF)对其的影响,以探讨脊髓小神经胶质细胞在糖尿病痛性周围神经病变中的作用.方法 采用腹腔注射链尿佐菌素(streptozotocine,STZ)诱导糖尿病痛性周围神经病变大鼠模型,在造模成功的痛过敏糖尿病大鼠中取20只随机分为模型组(Ⅱ组,n:10)和PPF治疗组(Ⅲ组,n=lO),另取10只同月龄大鼠为空白对照组(Ⅰ组,n=10).Ⅲ、Ⅱ组在第28天后分别每天腹腔注射10 mg/kg的PPF和等剂量的生理盐水一周.于注射STZ前、注射STZ后2 d、7 d、14 d、21 d、28 d、35 d测量大鼠体重并取尾静脉血测定血糖;注射STZ前、注射STZ后7 d、14 d、21 d、28 d、35 d用von Frey丝测定50%机械缩足反应阈值(me-chanical withdraw threshold,MWT);注射STZ 35 d后处死大鼠,采用免疫组化的方法检测大鼠脊髓的补体受体3(CR3)变化情况.结果 与Ⅰ组相比,注射STZ后2 d Ⅱ、Ⅲ组血糖显著增高(P<0.01),注射STZ后35 d Ⅱ、Ⅲ组体重明显轻于Ⅰ组(P<0.01);MWT的变化:与Ⅰ组相比,注射STZ后28 d、35 d Ⅱ组和Ⅲ组MWT明显降低(P<0.01);与Ⅱ组相比,注射STZ后35 d Ⅲ组MWT升高(P<0.05).注射STZ后第35天检测大鼠脊髓的CR3变化:与Ⅰ组相比,注射STZ后35 d Ⅱ、Ⅲ组明显增多(P<0.01);与Ⅱ组相比,注射STZ后35 d Ⅲ组CR3明显减少(P<0.01).结论 糖尿病痛性周围神经病变大鼠脊髓小神经胶质细胞增殖活化,可能参与了糖尿病周围神经痛的形成;腹腔注射PPF可扭转其的作用.