Osmotic opening of the blood-brain barrier to methotrexate in the rat

Osmotic opening of the blood-brain barrier in the rat, by intracarotid infusion of 1.6 molal (m) arabinose solution, increases cerebrovascular permeability to 3H-methotrexate by a factor of about seven. PA (product of permeability and capillary surface area) increases from a mean of 3.3 X 10(-5) sec-1 in brains of control rats to as much as 28 X 10(-5) sec-1 at the cerebral hemisphere ipsilateral to carotid infusion. If tracer is introduced into the carotid artery after osmotic treatment, brain uptake is increased by a net factor of 50 (a factor of 70 due to elevation of PA, multiplied by 7 due to infusion by the carotid route) as compared to uptake by normal, untreated brain with infusion into a peripheral vein. Osmotic barrier opening followed by carotid drug administration may be of use in experimental chemotherapy of nervous system disease.