Introduction and history of anaesthesia-induced neurotoxicity and overview of animal models.

Brain development is initiated at around 3 weeks of gestation. The peak velocity of brain weight gain occurs around birth, with the neural circuitry subsequently being refined until at least 20 years of age. Antenatal and postnatal general anaesthesia suppresses neuronal firing during this critical period and may therefore impair brain development, referred to as "anaesthesia-induced neurotoxicity". Whilst up to 1% of children are exposed to general anaesthesia antenatally (e.g., as an innocent bystander to maternal laparoscopic appendectomy), 15% of children under 3 years of age undergo general anaesthesia postnatally (e.g., otorhinolaryngologic surgery). In this article, the history of preclinical and clinical research in anaesthesia-induced neurotoxicity will be reviewed, starting from the pioneering preclinical study in 1999 until the most recent systematic reviews. The mechanisms of anaesthesia-induced neurotoxicity are introduced. Finally, an overview of the methods used in preclinical studies will be provided, with a comparison of the different animal models that have been employed to investigate this phenomenon.