Influence of Dexmedetomidine on Toxicity of Intrathecal Ketamine on Neonatal Rat Spinal Function

Abstract

Purpose: To investigate the influence of dexmedetomidine on the effect of ketamine on developing spinal cord.Methods: Postnatal day 3 (P3) and postnatal day 7 (P7) rat pups received intrathecal ketamine (10 mg/kg b.wt) and/or dexmedetomidine (10 μg/kg b.wt). Spinal reflex function was assessed by evaluating the sensory stimuli based on mechanical withdrawal threshold. Spinal tissue was analysed for activated caspase-3 using monoclonal anti-activated caspase-3. Apoptosis count of the spinal tissue was also measured by Fluoro-Jade C staining while glial reactivity was assessed by ionized calcium binding adapter molecule 1 on Day 7 day following injection. Long-term spinal function in rat pups on postnatal day 35 (P35) was evaluated by measuring the hindlimb withdrawal threshold and gait analysis.Results: Exposure to intrathecal ketamine at 10 mg/kg in P3 and P7 pups decreased mechanical withdrawal thresholds and increase apoptosis and microglial activation in the spinal cord. Altered spinal function, as presented by a decrease in mechanical withdrawal threshold and altered static gait, was observed in P35 rats exposed to intrathecal ketamine on P3. Dexmedetomidine administration did not alter the spinal function and histology of spinal tissue. Co-administration of dexmedetomidine and ketamine suggests that the former reduced apoptosis counts, altered glial responses, increased mechanical withdrawal threshold and improved gait.Conclusion: Dexmedetomidine protects against intrathecal ketamine-induced spinal toxicity in neonatal rats.Keywords: Dexmedetomidine, Intrathecal ketamine, Spinal toxicity, Mechanical withdrawal threshold,Glial reactivity, Gait analysis, Activated caspase-3, Apoptosis count