Hyperammonaemia reduces intracellular 22Na (sodium) ion and extracellular 86Rb ion concentrations in the blood-brain barrier of the rat

Abstract

Ammonia may be the major cerebral intoxicant responsible for the increased general or passive permeability of the blood-brain barrier (BBB) leading to the cerebral edema associated with acute liver failure. The present study investigated the effects of ammonia, as NH4+, on Na+ (22Na), K+ (86Rb), and 14C-mannitol uptake in the BBB. An in situ isolated perfused rat brain preparation was used to study the action of 1 mM ammonium acetate in Krebs'-Ringer perfusate. Passive water transport in the brain was studied by 14C-labeled mannitol uptake, a usually nondiffusible marker and active water transport by 22Na and 86Rb uptake. NH4+ significantly reduced 14C-mannitol uptake into the choroid plexus (P < 0.001) and increased it in the CSF (P < 0.05). Decreased 86Rb was measured in whole brain (P < 0.01) and CSF. However, no effect was observed in brain parenchyma, endothelium or choroid plexus thereby suggesting an increased efflux of 86Rb to the interstitial fluid. NH+ increased Na+ uptake into all areas of the brain studied. NH4+ does not increase the passive permeability into the BBB and was decreased in the choroid plexus. The increased 22Na+ uptake was substantiated by the observed decreases in 86Rb uptake in whole brain and CSF. This suggested NH4+ stimulates the Na+/K+ pump and increases extracellular Na+ concentrations and possibly intracellular concentrations with a concomitant decrease in K+ concentrations. These observations may provide a basis for the explanation of NH+ toxicity during hepatic encephalopathy and liver failure-induced cerebral edema.