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A Blood-Brain Barrier Disruption Model Eliminating the Hemodynamic Effect of Ketamine

Published online by Cambridge University Press:  16 February 2016

David Fortin ,
Robert Adams  and
Ariane Gallez
David Fortin*
Affiliation:
Departments of Neurosurgery and Neuro-oncology, University of Sherbrooke Hospital, Sherbrooke, Quebec, Canada
Robert Adams
Affiliation:
Department of Neurosurgery, University of Sherbrooke Hospital, Sherbrooke, Quebec, Canada
Ariane Gallez
Affiliation:
Department of Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada
*
Departments of Neurosurgery and Neuro-oncology, University of Sherbrooke Hospital, Sherbrooke, Quebec, J1H 5N4, Canada.
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Abstract

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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.

Conclusion:

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.

Type
Experimental Neurosciences
Information
Canadian Journal of Neurological Sciences , Volume 31 , Issue 2 , May 2004 , pp. 248 - 253
Copyright
Copyright © The Canadian Journal of Neurological 2004

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