Tachi Keitaro, Fukuda Taeko, Tanaka Makoto
Department of Anesthesiology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
Department of Anesthesiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Heliyon. 2021 Feb 12;7(2):e06218. doi: 10.1016/j.heliyon.2021.e06218. eCollection 2021 Feb.
Postoperative cognitive dysfunction (POCD) is associated with poor quality of life and difficulty working. Its impact may be greater in middle-aged patients than in elderly patients. Neuroinflammation is reported to be a main cause of POCD. Olanzapine has been reported to improve learning and memory functions. We therefore investigated olanzapine's effectiveness and mechanisms in an adult rat POCD model.
Six-month-old rats underwent laparotomy and lipopolysaccharide (LPS group) or LPS + olanzapine (OLA group) intraperitoneal injection or anesthesia alone (CON group) 1 week after a Barnes maze training session. A Barnes maze test trial was then conducted the day after surgery or anesthesia. The microglial activity in the hippocampus and cytokine levels were measured by Iba1 staining and enzyme-linked immunosorbent assay, respectively.
The OLA group had significantly higher success rates of Barnes maze trial than the LPS group. The success rate in time of the OLA group was inferior to that of the CON group. On the other hand, the success rate in distance of the OLA group was similar to that of the CON group. Iba1 staining areas in the LPS and OLA groups were larger than that in the CON group; however, the staining area in the OLA group was smaller than that of the LPS group. Plasma interleukin-1β concentration in the LPS and OLA groups was significantly higher than that in the CON group; however, there was no significant difference between the LPS and OLA groups.
Olanzapine attenuated both spatial cognitive dysfunction and microglial activity of the hippocampus, which were induced by surgery and LPS injection. These effects were unrelated to inflammatory cytokine concentrations in plasma and hippocampus.
术后认知功能障碍（POCD）与生活质量差和工作困难有关。其影响在中年患者中可能比老年患者更大。据报道，神经炎症是POCD的主要原因。据报道，奥氮平可改善学习和记忆功能。因此，我们在成年大鼠POCD模型中研究了奥氮平的有效性和作用机制。
6个月大的大鼠在进行巴恩斯迷宫训练1周后，接受剖腹手术，然后腹腔注射脂多糖（LPS组）或LPS+奥氮平（OLA组），或仅接受麻醉（CON组）。术后或麻醉后第二天进行巴恩斯迷宫测试试验。分别通过Iba1染色和酶联免疫吸附测定法测量海马中的小胶质细胞活性和细胞因子水平。
OLA组巴恩斯迷宫试验的成功率明显高于LPS组。OLA组在时间上的成功率低于CON组。另一方面，OLA组在距离上的成功率与CON组相似。LPS组和OLA组的Iba1染色面积大于CON组；然而，OLA组的染色面积小于LPS组。LPS组和OLA组血浆白细胞介素-1β浓度明显高于CON组；然而，LPS组和OLA组之间没有显著差异。
奥氮平减轻了由手术和LPS注射诱导的空间认知功能障碍和海马小胶质细胞活性。这些作用与血浆和海马中的炎性细胞因子浓度无关。
