Abstract
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 (GABAA) 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 GABAA 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.
Highlights
Post-operative cognitive dysfunction (POCD) is featured with cognitive decline, such as memory and executive functions after surgeries, including thyroid cancers, especially in elderly patients
Our study validated the previous findings by highlighting the involvement of gamma-amino butyric acid type A (GABAA) receptor α5 in the anesthetics-induced POCD
The mouse model used here has been verified by several recent studies from other groups by using single dose of etomidate, which caused memory and cognitive impairment, POCD [3, 7]
Summary
Post-operative cognitive dysfunction (POCD) is featured with cognitive decline, such as memory and executive functions after surgeries, including thyroid cancers, especially in elderly patients. It could last days, weeks, and months even longer than several years [1]. Statistical data suggest that the proportion of POCD after surgery in elderly patients is as high as 10% at 3 months after surgery [2]. Multiple factors are considered to predispose POCD, such as aging and other pre-existing medical conditions [4]. The underlying mechanisms of this disorder remain ambiguous so far. Few options of the treatment are for POCD so far due to lack of the extensive knowledge of this disorder. Recent studies indicated that the type of anesthetics, anesthetic method, and the duration of anesthetics were critical factors that contributed
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