Propofol Reverses Surgery-Induced Neuroinflammation and Cognitive Impairment in Aged Mice via α5-GABAA Receptors

Abstract

Surgery may lead to long-lasting cognitive deficits that are referred to as perioperative neurocognitive disorder (NCD), particularly in elderly patients. Currently, no interventions are routinely employed in clinical practice to prevent perioperative NCD. Here we show that perioperative chronic intermittent administration of propofol to aged mice undergoing laparotomy under isoflurane anesthesia effectively blocks the surgery-induced increase in nitrosative stress, increased expression of proapoptotic proteins, microglial activation, and cognitive deficits. By contrast, in the absence of surgery and anesthesia, propofol had little effect on biochemical parameters and led to cognitive improvement only in a subset of behavioral paradigms. The actions of propofol were largely absent in mice lacking the GABAA receptor 5-subunit, indicating that they are mediated by 5-containing GABAA receptors. These results demonstrate that propofol - via 5-containing GABAA receptors that are redistributed to the cell surface membranes in a sustained manner - can attenuate surgery-induced neuroinflammation and postsurgical cognitive deficits.