General Anesthetic-Induced Neurotoxicity in the Immature Brain: Reevaluating the Confounding Factors in the Preclinical Studies

Abstract

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.

Ferroptosis involved in sevoflurane-aggravated young rats brain injury induced by liver transplantation

“…Previous studies have shown that 1.5 MAC sevoflurane inhalation for 2 h potentiated surgery impaired cognitive function [ 27 ]. Prolonged (6–9 h) exposure to high concentrations (3–4%) of sevoflurane causes neuroinflammation and neuronal apoptosis and leads to long-term cognitive impairment [ 28 ]. Exposure to sevoflurane increased iron content in hippocampal neurons compared with cells not exposed to sevoflurane [ 29 ].…”

Neuron-Glia Crosstalk Plays a Major Role in the Neurotoxic Effects of Ketamine via Extracellular Vesicles

“…Designing protective measures or alternative anesthetics require the understanding of the mechanisms that mediate GA neurotoxic effects. Although various studies aiming to delineate pathways that mediate these processes were reported in the last several years, most of them were performed in rodents ( Jevtovic-Todorovic, 2016 ; Lin et al, 2017 ; Luo et al, 2020a ).…”