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

Ketamine and dexmedetomidine are increasingly used in combination in pediatric patients. This study examined the hypothesis that dexmedetomidine attenuated ketamine-induced neurotoxicity.

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.

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.

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.