Introduction: Traumatic brain injury has been shown to involve secondary injury pathways including autonomic dysregulation, ischemia, and excitotoxicity leading to neuronal death. Dexmedetomidine is an alpha-2 agonist that has demonstrated neuroprotection in animal models for ischemia and excitotoxicity. There have been no published reports of dexmedetomidine's effectiveness in neuroprotection following traumatic brain injury.
Methods: Controlled cortical impact through a pneumatic device was used to create a moderate head injury in 8 week-old mice. The mice were randomized to receive either saline or dexmedetomidine at 1ug/kg, 10ug/kg, or 100ug/kg doses at 1 hour and 12 hours after injury. Mice were sacrificed at 24 hours after injury. Histopathological analysis was carried out using Fluoro Jade-B and cresyl violet staining. Fluoro Jade-B staining was used to mark neuronal death in the dentate gyrus. Cresyl violet staining allowed for quantification of ischemic damage to the cortex.
Results: There was significantly less neuronal death at 1ug/kg and 100ug/kg dexmedetomidine compared to saline (p < 0.05). There was significantly less ischemic damage in the cortex at 10ug/kg, but not at 1ug/kg or 100ug/kg doses (p < 0.05).
Conclusions: Dexmedetomidine demonstrated neuroprotection in a in vivo murine model for TBI. Dexmedetomidine deserves further research to determine if these results can be duplicated in other animal models and possibly applied to humans.
Patient Care: Dexmedetomidine is a FDA-approved sedative that has a histopathological neuroprotective effect in multiple ischemic and excitotoxic animal models and now in a TBI animal model. Dexmedetomidine deserves further research to see if this neuroprotection potentially carries over to improved clinical outcomes in humans.
Learning Objectives: At the end of the presentation, participants will understand the potential role for dexmedetomidine in traumatic brain injury.