title: Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury.
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.
  
  
  CONCLUSIONS
  In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.
authors.affiliation: Department of Anesthesiology, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schoeler
authors.forename: Philip D
authors.initials: PD
authors.lastname: Loetscher
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Astrid V
authors.initials: AV
authors.lastname: Fahlenkamp
authors.forename: Georg
authors.initials: G
authors.lastname: Eberhardt
authors.forename: Steffen
authors.initials: S
authors.lastname: Rex
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000473:pathology / Q000517:prevention & control*; D002452:Cell Count; D020927:Dexmedetomidine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007036:Hypothermia, Induced / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D018696:Neuroprotective Agents; D020927:Dexmedetomidine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one