Insulin signaling in the central nervous system, a possible pathophysiological mechanism of anesthesia-induced delayed neurocognitive recovery/postoperative neurocognitive disorder: a narrative review.

INTRODUCTION: Impairment in neurocognitive functions ranges between delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorders (pNCD). Incidence varies from 11% after non-cardiac surgery to 60% after cardiac surgery. AREAS COVERED: Insulin receptors (IRs) signaling pathway in the central nervous system (CNS) could be a possible pathophysiological mechanism of anesthesia-induced DNR/pNCD and perioperative intranasal insulin administration could be a preventive approach. This hypothesis is supported by the following evidence: effects of IRs-CNS signaling pathway on neuronal survival, neuroprotection and neuromodulation; higher incidence of DNR/pNCD in patients who presented insulin resistance; neurotoxicity induced to IRs signaling pathways after exposure to general and local anesthetics; improvement of neurocognitive impairment after insulin exposure. This narrative review was conducted after a literature search of PubMed, EMBASE and SCOPUS online medical data performed in May 2022. The following search terms were used: insulin receptors in peripheral tissues, insulin receptors and brain, postoperative neurocognitive impairment, insulin resistance and cognitive impairment, insulin receptors and anesthesia exposure, intranasal insulin and postoperative cognitive impairment. EXPERT OPINION: Perioperative intranasal insulin is shown to be protective and future studies should address: the role of insulin as a neuromodulator; its integration into neuroprotection approaches; patient populations that might benefit from this approach; a well-defined protocol of intranasal insulin administration in a perioperative background and other disciplines; and possible collateral effects.