Technique for Repeatable Hyperosmotic Blood-Brain Barrier Disruption in the Dog
Culver, Britt Wayne
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Reversible hyperosmotic blood-brain barrier disruption (BBBD) has been used in pharmaceutical research as well as human medicine to enhance drug delivery across the blood-brain barrier. However a technique for repeatable BBBD in the canine has not been described. This study describes a repeatable technique for BBBD in the dog and evaluates the clinical and morphological effects of BBBD. Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery in ten dogs. BBBD was achieved in 5 dogs using 25% mannitol while 5 control dogs received only saline. Following recovery, dogs were monitored for clinical signs before a second, non-survival procedure was performed 2-3 weeks later. BBBD was estimated using CT densitometry as well as Evan's blue staining on post-mortem exam. Histopathological evaluation of the brain was performed on all dogs. Seven dogs completed the study. Two treatment dogs were lost after the first infusion with deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost due to vessel wall damage during catheterization. The remaining dogs exhibited only transient neurologic, ocular, and vasculature injury. Successful BBBD was demonstrated in all treatment dogs as evidenced by CT and Evan's blue staining. Histopathological evaluation revealed multifocal areas of infarction in all dogs indicating refinement of the technique is needed. This study shows that repeatable disruption the BBB in the dog is possible and opens the way for further investigations of BBBD using the dog as a model.
- Masters Theses