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 per meability, the albumin content was determined in the cerebrospinal flu id and in the brain 1 h after intracarotid infusion of protamine sulph ate, a natural polycationic protein with a high content of arginine (m ol. wt 4000-4400), poly-L-arginine (mol. wt 11600) or poly-L-lysine (m ol. wt 10200). Five milligrams (4 x 10(-4) mmol) poly-L-arginine incre ased 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 a nd 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 0.3 0, 0.46 and 1.21 mg ml-1 in rats given 5 Mg poly-L-lysine, protamine a nd poly-L-arginine, respectively (P < 0.01 for difference between argi nine and the other two substances). The higher mol. wt and positive ch arge of poly-L-arginine may at least in part explain the more pronounc ed albumin leakage after arginine than after protamine. However, the d ifference between poly-L-arginine and poly-L-lysine suggests that othe r factors, possibly related to the guanidino groups, contribute to the blood-brain barrier opening by poly-L-arginine.