Altering the blood-brain barrier in the rat by intracarotid infusion of polycations: a comparison between protamine, poly-L-lysine and poly-L-arginine.

To evaluate the role of surface charge for the blood-brain barrier permeability, the albumin content was determined in the cerebrospinal fluid and in the brain 1 h after intracarotid infusion of protamine sulphate, a natural polycationic protein with a high content of arginine (mol. wt 4000-4400), poly-L-arginine (mol. wt 11,600) or poly-L-lysine (mol. wt 10,200). Five milligrams (4 x 10(-4) mmol) poly-L-arginine increased the albumin content in the brain 15 times more than 5 mg (5 x 10(-4) mmol) poly-L-lysine (P < 0.001) and 3.5 times more than 5 mg (1 x 10(-3) mmol) protamine (P < 0.001); the difference between protamine and poly-L-lysine was also significant (P < 0.05). After 0.5 mg (4 x 10(-4) mmol) poly-L-arginine the albumin extravasation was still higher than after 5 mg protamine (P < 0.01) and 5 mg poly-L-lysine (P < 0.001). Cisternal albumin increased from control values 0.08 mg ml-1 to 0.30, 0.46 and 1.21 mg ml-1 in rats given 5 mg poly-L-lysine, protamine and poly-L-arginine, respectively (P < 0.01 for difference between arginine and the other two substances). The higher mol. wt and positive charge of poly-L-arginine may at least in part explain the more pronounced albumin leakage after arginine than after protamine. However, the difference between poly-L-arginine and poly-L-lysine suggests that other factors, possibly related to the guanidino groups, contribute to the blood-brain barrier opening by poly-L-arginine.