Selective intra-arterial infusion of protamine sulphate for transient blood-brain barrier opening in rats

Abstract

To determine the appropriate dose of protamine sulphate (PS) for blood-brain barrier (BBB) opening and its effect, commercially available 1% PS solution was administered into the internal carotid artery of the rats. The degree of BBB disruption was evaluated as a blue stain in the brain following intravenous injection of 2% Evans’s blue solution. Three rats were observed for 1 week after 1 ml of PS infusion to examine neurological signs. The following results were obtained: at least 1.0 ml of PS was necessary for BBB opening in this rat model; 1.0 ml of PS opened the BBB transiently for approximately 60 min and no BBB changes were detected 90 min after PS injection; PS-infused rats did not show any neurological deficits. Intra-arterially infused 1.0 ml PS opened the BBB for approximately 60 min. Superselective intra-arterial infusion of PS may provide a useful method for delivering the chemical agent into the brain.