Neonatal Anaesthesia and Neuronal Injury: Molecular Mechanisms and Insights

Despite widespread use of general anaesthesia (GA) in neonatal procedures, its effects on the developing brain are still not fully understood, raising ongoing questions in both research and clinical practice. Experimental studies have demonstrated that GA can cause neuronal cell injury, and neonates may be vulnerable due to their physiological immaturity, necessitating exact dosing and constant monitoring. To optimise anaesthesia protocols and minimise risks in this vulnerable population, it is imperative to thoroughly evaluate the mechanisms underlying anaesthesia-induced neuronal cell damage in neonates. This review article will explore the following mechanisms: apoptosis, pyroptosis, gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA), oxidative stress and mitochondrial damage, calcium imbalance, neural circuit impairment, and neuroinflammation, with particular focus on studies utilising animal models. It will also highlight recent studies on therapeutic strategies against reducing neuronal cell damage. However, as most of these findings remain preclinical, their translational potential requires cautious interpretation. In conclusion, although current evidence highlights plausible mechanisms and emerging neuroprotective approaches, more clinical trials are needed to ensure the reliability and efficacy of the treatment strategies to confirm their effects on neonatal anaesthesia-induced cell damage.