The impact of dexmedetomidine on ketamine-induced neurotoxicity and cognitive impairment in young mice.

Abstract

The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity. In vitro experiments employed concentrations of 0.1uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3days (P7-P9) using dosages of 100 mg/kg for ketamine and 1mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively. Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine. This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities.