Wang Bin, Li Siyuan, Cao Xipeng, Dou Xinghui, Li Jingzhu, Wang Ling, Wang Mingshan, Bi Yanlin
Department of Anesthesiology, Qingdao Municipal Hospital, NO. 5 Donghai Middle Road, Qingdao, Shandong, 266071, China.
Department of General surgery, Qingdao Municipal Hospital, NO. 5 Donghai Middle Road, Qingdao, Shandong, 266071, China.
Curr Neurovasc Res. 2017;14(4):359-367. doi: 10.2174/1567202614666171009105825.
Postoperative Cognitive Dysfunction (POCD) has received considerable attention as one of the main postoperative complications. The underlying mechanism of POCD in elderly subjects has not been fully elucidated to date. The Central Nervous System (CNS) is isolated from the bloodstream by the Blood Brain Barrier (BBB) that consists of endothelial cells, capillary blood vessels and tight junctions. The tight junctions carry out significant biological functions that are associated with the CNS and blood circulation.
In this review, I present a hypothesis that blood-brain barrier disruption leads to postoperative cognitive dysfunction. A total of 81 healthy male Wistar rats were used for the present study. All the experimental animals were randomly divided into 3 groups: normal control group, isoflurane group and splenectomy group. The control group was not subjected to any form of treatment. The rats in isoflurane group were given 1.5-2% isoflurane under intubation and mechanical ventilation. The rats in splenectomy group underwent splenectomy under the same anesthesia as the isoflurane group. The Morris water maze was used to examine the learning and memory ability of the animals. The expression of the Tight Junctions Proteins (TJPs) in the hippocampus was analyzed using Western blotting. The concentration of Evans Blue (EB) in the supernatant was analyzed using UV spectroscopy. Ultrastructure changes in the basal laminas, the Tight Junctions (TJs), mitochondria and the endoplasmic reticulum surrounding the capillaries were assessed by Transmission Electron Microscopy (TEM).
Following splenectomy, the rats displayed concomitant significant cognitive deficits in the Morris water maze test. Taken together, the results indicate that the expression levels of occludin (65KD) following splenectomy were reduced on days one and three in aged rats. No significant difference was noted in the expression levels of claudin-5, except for a reduction after surgery on day one. The leakage of EB was higher following splenectomy than control group and isoflurane group. The ultrastructure of the neurovascular unit was monitored on the day prior to surgery and on the 1st, 3rd and 7th day following surgery using a transmission electronmicroscope.
The alterations in the levels of tight junction proteins following splenectomy may contribute to the BBB permeability increase, which in turn will induce postoperative cognitive dysfunction.
术后认知功能障碍（POCD）作为主要的术后并发症之一已受到广泛关注。迄今为止，老年患者POCD的潜在机制尚未完全阐明。中枢神经系统（CNS）通过由内皮细胞、毛细血管和紧密连接组成的血脑屏障（BBB）与血液循环隔离开来。紧密连接执行与中枢神经系统和血液循环相关的重要生物学功能。
在本综述中，我提出了一个假说，即血脑屏障破坏导致术后认知功能障碍。本研究共使用了81只健康雄性Wistar大鼠。所有实验动物随机分为3组：正常对照组、异氟烷组和脾切除组。对照组未接受任何形式的治疗。异氟烷组大鼠在插管和机械通气下给予1.5 - 2%异氟烷。脾切除组大鼠在与异氟烷组相同的麻醉下进行脾切除术。使用Morris水迷宫检测动物的学习和记忆能力。采用蛋白质免疫印迹法分析海马中紧密连接蛋白（TJPs）的表达。使用紫外光谱法分析上清液中伊文思蓝（EB）的浓度值。通过透射电子显微镜（TEM）评估毛细血管周围基膜、紧密连接（TJs）、线粒体和内质网的超微结构变化。
脾切除术后，大鼠在Morris水迷宫试验中表现出明显的认知缺陷。综合来看，结果表明老年大鼠脾切除术后第1天和第3天闭合蛋白（65KD）的表达水平降低。除术后第1天有所降低外，闭合蛋白-5的表达水平未观察到显著差异。脾切除术后EB的渗漏高于对照组和异氟烷组。在手术前一天以及手术后第1、第3和第7天，使用透射电子显微镜监测神经血管单元的超微结构。
脾切除术后紧密连接蛋白水平的改变可能导致血脑屏障通透性增加，进而诱发术后认知功能障碍。
