title: A blood-brain barrier disruption model eliminating the hemodynamic effect of ketamine.
abstract: OBJECTIVE
  We propose a simple modification to an established blood-brain barrier disruption (BBBD) animal model that allows us to use ketamine/xylazine as the anaesthetic agent, therefore decreasing the complexity and the cost of the model, while maintaining similar efficiency.
  
  
  METHODS
  Sixty-two Long Evans rats were anaesthetized by intraperitoneal injection of ketamine/xylazine. Osmotic BBBD was performed by administering 25% mannitol into the internal carotid artery in a retrograde fashion from the external carotid. The infusion rate of mannitol, as well as the duration was adjusted in a stepwise fashion to identify optimal parameters for BBBD and minimize complications. As a supplementary step to previously reported models, a vascular clip was applied to the common carotid artery prior to the infusion of mannitol, therefore isolating our model system from the depressant hemodynamic effects of ketamine/xylazine. Evans blue dye was used to control for BBBD intensity.
  
  
  RESULTS
  Using this model at an initial infusion rate of 0.15 ml/sec, a significant incidence of brain hemorrhage (75%) and a death rate of 62.5% were observed. Decreasing the infusion rate in a stepwise fashion, 0.08 ml/sec was found to produce optimal BBBD, as demonstrated by Evans blue staining. At this rate, 6/7 animals depicted grade II staining, whereas one animal depicted grade IV.
  
  
  CONCLUSIONS
  The application of a clip to the common carotid artery prior to mannitol infusion allowed us to isolate the cerebral circulation from the depressant hemodynamic effects of ketamine/xylazine. This supplementary step produced consistent and efficient BBBD in our animal model.
authors.affiliation: Department of Neurosurgery, University of Sherbrooke Hospital, Sherbrooke, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Fortin
authors.forename: Robert
authors.initials: R
authors.lastname: Adams
authors.forename: Ariane
authors.initials: A
authors.lastname: Gallez
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000778:Anesthetics, Dissociative / Q000008:administration & dosage; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004234:Diuretics, Osmotic / Q000008:administration & dosage; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage; D008353:Mannitol / Q000008:administration & dosage; D023421:Models, Animal; D051381:Rats; D020318:Rats, Long-Evans; D014991:Xylazine / Q000008:administration & dosage
chemical_list: D000316:Adrenergic alpha-Agonists; D000778:Anesthetics, Dissociative; D004234:Diuretics, Osmotic; D014991:Xylazine; D008353:Mannitol; D007649:Ketamine