Dexmedetomidine provides neuroprotection: impact on ketamine‐induced neuroapoptosis in the developing rat brain

Abstract

BACKGROUND: Ketamine and dexmedetomidine are increasingly used in combination in pediatric patients. This study examined the hypothesis that dexmedetomidine attenuated ketamine-induced neurotoxicity. METHODS: Neonatal rats were randomly divided into four groups (n=10, male 5, female 5). Group S+S received an equal volume of normal saline intraperitoneally and subcutaneously at an interval of 5 min. Group K+S received an intraperitoneal injection of 75 mg/kg ketamine followed by subcutaneous injection of normal saline 5 min later. Group S+D were given subcutaneously 25 μg/kg dexmedetomidine 5 min after injection of normal saline. Group K+D received a subcutaneous injection of 25 μg/kg dexmedetomidine 5 min after ketamine injection. The above drugs were given once daily for 3 days. Neuronal apoptosis in the CA1 region and the dentate gyrus of rats was examined by transferase dUTP nick end labeling (TUNEL) assays. Learning and memory abilities of 2-month old rats were examined by Morris water maze test. The results were analyzed by analysis of variance. RESULTS: The percentage of TUNEL-positive cells in group K+S (CA1, 49.0±9.46 and dentate gyrus, 49.4±5.41) was markedly higher than that in group K+D (CA1, 37.2±5.54 and dentate gyrus, 35.2±5.06) (F=5.49, P<0.05 and F=13.51, P<0.001, respectively). Group K+S took significantly longer time and swimming distance to find the hidden platform on the fourth and fifth training days than group K+D (P<0.05). Moreover, group K+D spent considerably more time in the target quadrant than group K+S (P<0.05). Dexmedetomidine alone caused a small but statistically insignificant increase in neuronal apoptosis of the CA1 region and the dentate gyrus of neonatal rats compared with normal saline. CONCLUSION: In conclusion, ketamine caused neuroapoptosis and impaired brain functions in the developing rat brain which can be effectively attenuated by dexmedetomidine. Dexmedetomidine alone was not neurotoxic to the developing brain.