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

ABSTRACT

Introduction

Impairment in neurocognitive functions ranges between delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorders (pNCD). Incidence varies from 11% after noncardiac 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 neuromodulation; higher incidence of DNR/pNCD in patients with insulin resistance; neurotoxicity of IRs signaling pathways after anesthetic exposure; 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.

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.

KEYWORDS:

• Insulin receptors
• brain
• postoperative cognitive impairment
• intranasal insulin
• neuromodulator-like action

Article highlights

• Incidence of postoperative neurocognitive impairment such as DNR and/or pNCD varies from 11% to 60%

• A causal association between anesthesia exposure and DNR/pNCD onset has been reported by preclinical and clinical studies

• Insulin receptors signaling pathway has a non-metabolic activity in the CNS and interferes with cognitive functions through a neuromodulator-like action

• Recent evidence suggests an interaction between anesthetics and insulin receptors signaling in the CNS and shows that perioperative intranasal insulin administration improves the outcome

• IRs signaling pathway might contribute to anesthesia-induced DNR/pNCD

• Future studies should address the role of intranasal insulin in neuroprotection, patient population that might benefit of this approach and a well-defined administration protocol.

Abbreviations list

Table

Author contributions

EQ: conception and design of the paper, interpretation of the relevant literature, writing and editing the manuscript. CS: conception and design of the paper, interpretation of the relevant literature, writing and editing the manuscript. FB: conception and design of the paper, interpretation of the relevant literature, writing and editing the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737175.2022.2144234

Additional information

Funding

This paper was not funded.