Developmental synaptogenesis and general anesthesia: a kiss of death?

Abstract

Normal cognitive development depends on the timely formation of meaningful neuronal circuitries. These, in turn, depend on the proper formation and functioning of neuronal synapses, which control the flow of information between neurons. The time period when synapse formation is most intense is referred to as synaptogenesis, coinciding with the peak of brain development. The latest animal and human research suggests that general anesthetics, which act by modulating the fine balance in neurotransmission, may disturb the fine homeostasis necessary for neuronal signaling, resulting in morphometric and functional disturbances of developing synapses in synaptogenesis. Anesthesia-induced impairment of synaptogenesis is strongly age-dependant. At a younger stage, neurons respond by decreasing synaptic densities. But in later development, they respond by overly upregulating synapse formation. Although a direct causal link between disturbed synaptogenesis and behavioral development is not yet established, several animal studies have confirmed that cognitive development of rodents and non-human primates could be permanently impaired after a single exposure to clinically-relevant general anesthetics. Clinical evidence is now beginning to emerge suggesting that very young children may be susceptible to anesthesia-induced impairment of behavioral development, cognitive in particular. This review will summarize some of the presently available evidence regarding anesthesia-induced effects on developmental synaptogenesis and intellectual functioning.