Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury

BMC Neurol. 2012 Apr 11:12:20. doi: 10.1186/1471-2377-12-20.

Abstract

Background: The α2-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an in vitro model for traumatic brain injury.

Methods: Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.

Results: Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.

Conclusion: In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Cell Count
  • Dexmedetomidine / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enzyme Inhibitors / therapeutic use
  • Flavonoids / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hypothermia, Induced / methods
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / therapeutic use*
  • Organ Culture Techniques
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Neuroprotective Agents
  • Dexmedetomidine
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one