Osmotic blood-brain barrier disruption in the posterior fossa of the dog

Transient reversible osmotic blood-brain barrier disruption was produced in the posterior fossa of 33 dogs. A percutaneous catheter technique was used for the infusion of hypertonic mannitol into the vertebral artery. Neither the catheter technique nor the osmotic barrier modification resulted in interference with brain-stem function in most animals. The degree of barrier modification achieved by osmotic disruption in the posterior fossa is similar to that previously described for barrier modification of the supratentorial parenchyma. Methotrexate delivered to the brain via the vertebral artery resulted in a drug concentration of 100 to 300 ng/gm brain tissue. When the same amount of drug was given following osmotic blood-brain barrier disruption, brain tissue contained 1100 to 5000 ng of methotrexate/gm of brain tissue. Finally, the adequacy of the blood-brain barrier modification in the posterior fossa was shown to be quantifiable by the amount of enhancement on computerized tomographic scans.