Indian Journal of Anaesthesia, July 25, 2013.
S Bala Bhaskar Department of Anaesthesiology and Critical Care, Vijayanagar Institute of Medical Sciences, Bellary, Karnataka, India
Millions of surgeries and procedures are performed world-wide in children and sedatives and anaesthetic agents have sometimes been used with impunity in these cases. The modern anaesthetic agents have good safety profiles as far as the immediate goals of anaesthesia and post-operative period are concerned. Increasingly, concerns have cropped up on their long-term adverse effects on the neural structure and neurocognitive function, more so in neonates and infants. Much of the evidence is based on animal studies (preclinical) and few retrospective human clinical studies; human prospective clinical studies are few.
What is known is that the anaesthetics exert their effects by action on multiple receptors and ion channels in the central nervous system. Intravenous agents are more potent than the inhalational agents but have similar effects on the various receptors and channels involved in anaesthesia. It is also known that anaesthetics induce neuroapoptosis, an active programmed cell death.  It could involve promotion of the physiological apoptosis or induction of pathological apoptosis. Spurt in brain growth or synaptogenesis occurs in early postnatal period in the majority of experimental animals and in humans, it starts in mid- gestation and extends for few years into childhood. The risk of damage to neuronal tissue is therefore, maximum during this period. Inhibitions of brain-derived neurotrophic factor (BDNF) signalling pathways by agents with N-methyl-D-aspartate glutamate (NMDA) receptor antagonism, or γ-amino-butyric acid (GABA) type. Receptor agonism or both (ethanol) are associated with extensive neuronal apoptosis in animal models. , BDNF is essential for growth, differentiation and survival of neuronal tissue. Other proposed neural effects of these agents include alteration in dendritic spine architecture. 
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