Li Liang, Zhang Chunhai
Department of Orthopedics, Shenzhen Hospital, South Medical University, Shenzhen, China.
Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Front Neurol. 2021 Feb 23;12:591223. doi: 10.3389/fneur.2021.591223. eCollection 2021.
Post-operative cognitive dysfunction (POCD) is a common complication during the post-operative period. It affects the recovery time of the patient after surgery and the stay time in hospital, which causes a great deal of burden to patients and families emotionally and financially. However, there is no specific and effective treatment available for this disorder. Recent study indicated exposure to general anesthetics contributed to POCD by triggering gamma-amino butyric acid type A (GABA) receptors hyperactivities that persisted even the anesthetic compounds have been eliminated. Here, we investigated the antidepressant, venlafaxine (VLX), in a mouse model of POCD and studied whether VLX attenuated the cognitive dysfunction of mice exposed to general anesthetic, isoflurane (ISO). We found that ISO significantly induced an increased surface expression of the GABA receptor subunit, α5, in the hippocampus of the mice. However, VLX treatment reduced the increase in α5 subunit expression. Meanwhile, we found the expression levels of interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), and IL-6 in the brains of mice exposed to ISO were significantly increased. However, VLX could prevent the increase in these cytokines. We also investigated the memory deficit of these mice by using a Y maze behavioral test. Mice with ISO exposure showed decreased alternation performance that could be prevented by the VLX treatment. Collectively, our results here are in line with the previous findings that α5 subunit plays an important role of the formation of POCD, but VLX may be a promising candidate compound for the treatment of POCD.
术后认知功能障碍（POCD）是术后常见的并发症。它会影响患者术后的恢复时间和住院时间，给患者及其家庭带来巨大的情感和经济负担。然而，目前尚无针对这种疾病的特异性有效治疗方法。最近的研究表明，全身麻醉药的暴露通过触发A型γ-氨基丁酸（GABA）受体的过度激活导致POCD，即使麻醉药物已被清除，这种过度激活仍会持续。在此，我们在POCD小鼠模型中研究了抗抑郁药文拉法辛（VLX），并研究了VLX是否能减轻暴露于全身麻醉药异氟烷（ISO）的小鼠的认知功能障碍。我们发现，ISO显著诱导小鼠海马中GABA受体亚基α5的表面表达增加。然而，VLX治疗可降低α5亚基表达的增加。同时，我们发现暴露于ISO的小鼠大脑中白细胞介素（IL）-1β、肿瘤坏死因子α（TNF-α）和IL-6的表达水平显著升高。然而，VLX可以阻止这些细胞因子的增加。我们还通过Y迷宫行为测试研究了这些小鼠的记忆缺陷。暴露于ISO的小鼠表现出交替行为减少，而VLX治疗可预防这种情况。总的来说，我们的研究结果与之前的发现一致，即α5亚基在POCD的形成中起重要作用，但VLX可能是一种有前途的POCD治疗候选化合物。
