CHANGES IN THE PERMEABILITY OF THE BLOOD - BRAIN BARRIER IN ACUTE HYPERAMMONEMIA - EFFECT OF DEXAMETHASONE

This study was designed to determine the contribution of elevated plas ma ammonia levels to blood-brain barrier (BBB) abnormalities in the pr esence of intact liver. The permeability changes of the BBB were inves tigated grossly with Evans blue (EB) and quantitatively by measuring t he blood-to-brain transfer content for alpha-aminoisobutyric acid (AIB ) in normal rats and rats subjected to sublethal doses of ammonium ace tate (NH4OAc) (750 and 600 mg/kg ip; at 30-min intervals). Some rats w ere pretreated with dexamethasone (DXN). Injection of NH4OAc increased both plasma and brain ammonia concentrations about 16-and 5-fold, res pectively, above the control level. In rats receiving NH4OAc injection , the blood-to-brain transfer constant (K(i)) for AIB was increased 3- to 11-fold. The elevated K(i) values were limited to certain gray mat ter areas and less pronounced permeability changes were detected in wh ite matter. Extravasation sites of EB were more restricted and were es pecially observed in thalamus and cerebellum, whereas cortex and white matter were unaffected. Dexamethasone pretreatment for 3 d reduced bo th leakage of EB and the K(i) for AIB in NH4OAc injected animals, wher eas acute treatment appeared ineffective. Dexamethasone did not preven t the development of coma but slightly decreased the ammonia concentra tion in plasma and brain. The results obtained indicate that hyperammo nemia may disrupt BBB integrity not only to AIB and EB but also enhanc e the transport of other solutes.