Melatonin reduces the severity of anesthesia-induced apoptotic neurodegeneration in the developing rat brain: A-371

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Excerpt

Background and Goal of Study: General anesthetics cause widespread apoptotic neurodegeneration in many regions of the developing rat brain (1). We studied the neuroprotective effect of melatonin against the neurotoxic effect of anesthetic agent.
Materials and Methods: 7-day-old rats were exposed to 2, 4, 6 hrs of a commonly used and highly pro-apoptotic anesthesia cocktail (midazolam, isoflurane, nitrous oxide) in combination with the escalating doses of melatonin (from 1 to 20 mg/kg.s.c). We performed histopathological studies (silver staining, caspase staining) and Western blot studies (cytochrome c, bcl-xl).
Results and Discussions:
Conclusion(s): Melatonin-induced neuroprotection was mediated, at least in part, via the inhibition of the intrinsic pathway since melatonin caused an upregulation of the anti-apoptotic protein, bcl-xl, reduction in anesthesia-induced cytochrome c release into the cytoplasm and a decrease in anesthesia-induced activation of caspase-3, an important step in the activation of DNAses and the formation of the apoptotic bodies.
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