Abstract
Exposure to general anesthetics (GAs) and antiepileptics during critical stages of brain development causes significant neurotoxicity to immature neurons. Many animal, and emerging human studies have shown long-term functional sequelae manifested as behavioral deficits and cognitive impairments. Since GAs and antiepileptic drugs are a necessity, current research is focused on deciphering the mechanisms responsible for anesthesia-induced developmental neurotoxicity so that protective strategies can be devised. These agents promote massive and wide-spread neuroapoptosis that is caused by the impairment of integrity and function of neuronal organelles. Mitochondria and endoplasmic reticulum are particularly vulnerable. By promoting significant release of intracellular calcium from the endoplasmic reticulum, anesthetics cause an increase in mitochondrial calcium load resulting in the loss of their integrity, release of pro-apoptotic factors, functional impairment of ATP synthesis, and enhanced accumulation of reactive oxygen species. The possibility that GAs may have direct damaging effects on mitochondria, resulting in the impairment of their morphogenesis, also has been proposed. This review will present evidence that neuronal organelles are critical and early targets of anesthesia-induced developmental neurotoxicity.
Highlights
Rapid advances in pediatric anesthesiology and neurology have resulted in numerous exposures of the children to a variety of psychotropic agents that modulate neuronal activity
We have suggested that significantly fewer mitochondria are located in presynaptic neuronal profiles in anesthesia-treated brain than are in controls (Sanchez et al, 2011)
Melatonin, a naturally occurring sleep hormone that upregulates bcl-xL (Yon www.frontiersin.org et al, 2006) and prevents cytochrome c leak, and carnitine, a nutritional supplement that protects mitochondrial integrity (Zou et al, 2008), cause significant protection against neuronal apoptosis. It remains to be determined whether melatonin and carnitine protect against anesthesia-induced cognitive impairment, it is clear that mitochondria play an integral role in proper development of the immature neurons and their synaptic connections
Summary
Rapid advances in pediatric anesthesiology and neurology have resulted in numerous exposures of the children to a variety of psychotropic agents that modulate neuronal activity. Jevtovic-Todorovic et al Organelles and anesthesia-induced developmental neurotoxicity vulnerability observed during early and late stages of synaptogenesis may vary (Yon et al, 2005; Rizzi et al, 2008).
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