Investigation of the effect of circadian rhythm on neurotoxic effect of isoflurane administration in newborn rats

Aim: Some drugs used for sedation and anesthesia procedures produce histopathologic central nervous system changes in juvenile animals. These observations have raised concerns regarding the use of these drugs in pediatric patients. The aim of this study is to investigate the possible effects of circadian rhythm on neurotoxicity triggered by isoflurane.Material and Methods: We have administered 1,5% concentration of isoflurane anesthesia for 6 hours to 7 day old infant rats as previously descibed in order to trigger apoptotic neurodegeneration. 26 newborn rats were involved and randomized to four groups. Rat pups were exposed to anesthesia between 07:00 am-01:00 pm (day group) and 07:00 pm-01:00 am (night group) and controls were exposed to room air during same time intervals. Two hours after cessation of isoflurane anesthesia rats were sacrificed for histopathological studies.Results: Histopathological studies have confirmed the neurotoxic effect of 1,5% concentration of isoflurane anesthesia in developing rat brain either in day or night groups (p<0.05). Neuroapoptotic response in thalamus paraventricular nucleus, cortex and hippocampus CA1 region was observed stronger in day group than night group (p<0.05).Conclusion: According to our findings we decided that there is a circadian rhythm in isoflurane neurotoxiciy and well designed clinical investigations are needed to assess the potential relevance of the animal findings to pediatric anesthesia.