Effects of topical isoproternol on blood-brain barrier permeability in cerebral cortex of rats

This study was performed to examine whether direct topical application of isoproterenol to the cerebral cortex could modify blood-brain barrier (BBB) permeability and whether the effect could be blocked bytimolol, a beta adrenergic receptor antagonist, without membrane stabilizing effects. After craniotomy, a low dose [10^-4M, n=6] or a high dose [10^-3M, n=6] isoproterenol patch was placed on one cortex (Ipsilateral Cortex: IC) and a normal saline patch was placed on the other cortex (Control Cortex:CC) in each animal. The other 6 animals were pretreated with timolol 1.5 mg/kg iv before placement of high dose isoproterenol patches. The BBB transfer coefficient (Ki) was determined using ¹⁴C-α-aminoisobutyric acid. Mean arterial blood pressure was lower in the animals given high dose isoproterenol compared to animals given timolol pretreatment. Low and high doses of isoproterenol increased the Ki by 58% and 66% respectively when compared to that of the corresponding CC: Low dose: IC:5.94±2.02, CC:3.77±1.73 μl/g/min High dose: IC:6.97±3.66, CC:4.19±2.48 μl/g/min Pretreatment with timolol prevented the increase of the Ki by high dose of isoproterenol (IC:5.33±1.88, CC:5.66±1.72). Our data suggest that beta adrenergic receptor agonists are involved in increasing the BBB permeability, and that this effect could be prevented with beta adrenergic receptor antagonists.