**6. General anesthesia and developing brain. A special highlight for neonatal anesthesia**

One of the most interesting topics in the last 20 years is the general anesthetic effect on the developing brain and neurocognitive functions.

Animal studies show that exposure to general anesthetics (especially these acting through the NMDA and GABA receptors) during the critical period of neuronal development in the developing brain leads to an apoptotic cell death and neurocognitive impairment especially in immature brain [39, 40]. It is reported that this effect to be related to drug dosages and exposure time.

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Long-term neurobehavioral effects of sedative and anesthetic agents should be supported by long-term human studies. In recent years, early results of international, multidisciplinary, prospective clinical trials such as GAS and PANDA have begun to be published [41, 42].

In these studies and in Wilder et al. study, it has been reported that multiple exposures to anesthesia, rather than single exposure to anesthesia, pose a risk factor for later development learning disability in children [41–43].

However, to withhold sedation and anesthesia when necessary, would result in ethical consequences, in addition will trigger many negative consequences of painful stimulation in neonatal patients.
