Reduction of Postoperative Cognitive Deficits in Aged Mice by Chronic Intermittent Propofol

Abstract

Postoperative cognitive dysfunction (POCD) can increase morbidity and mortality after surgery, especially in the elderly. Current evidence from both clinical/epidemiological studies and animal studies suggest that POCD is likely due to factors related to the surgery itself and at least not primarily due to the effects of general anesthetic agents. In contrast, propofol, the most commonly used intravenous general anesthetic agent which is acting mainly via GABAA receptors, has been shown to have neuroprotective effects by attenuating caspase activation, apoptosis, and mitochondrial dysfunction. We therefore set out to assess the effects of chronic intermittent propofol on postoperative cognitive deficits in aged mice. Abdominal surgery (exploratory laparotomy) under isoflurane anesthesia was performed in 21‐24 months‐old mice. Animals received either chronic intermittent propofol (75 mg/kg i.p.) or vehicle (IntralipidR) every 5th day throughout the experiment. The laparotomy was performed on day 17. Two days later, the mice were employed in the open field test. There was no difference in postoperative locomotor activity among groups (Surgery+Vehicle, Surgery+Propofol, No surgery+Vehicle, No surgery+Propofol). Then, cognitive functions were assessed using the Y maze, novel object recognition, contextual fear conditioning and Morris water maze tests. We found that laparotomy resulted in impaired learning and memory as determined in the behavioral test battery compared to no surgery controls. However, perioperative chronic intermittent propofol strongly attenuated the surgery‐induced memory impairments. Moreover, propofol per se improved the (likely age‐related) cognitive dysfunction in the no surgery controls. Our findings suggest that perioperative intermittent propofol administration might prevent or attenuate surgery‐induced cognitive dysfunction, and thus potentially reduce the liability for undesired long‐term outcomes. Thus, chronic intermittent administration of propofol may represent a novel therapeutic strategy with translational potential.