Role of ammonia in the pathogenesis of brain edema.

The role of hyperammonemia in the pathogenesis of cerebral edema was investigated using mongrel dogs to develop a treatment for cerebral edema in acute hepatic failure. Intravenous infusion of ammonium acetate alone into dogs did not induce brain edema, although blood ammonia reached unphysiologically high levels. However, ammonium acetate infusion during mannitol-induced reversible (osmotic) opening of the blood-brain barrier (BBB) effectively induced cytotoxic brain edema. Pretreatment with a branched-chain amino acid (BCAA; valine, leucine and isoleucine) solution prevented an increase in intracranial pressure (ICP) and brain water content, and caused a decrease in brain ammonia content and an increase in brain BCAA and glutamic acid. The results suggest that ammonia plays an important role in the pathogenesis of cerebral edema during acute hepatic failure and that BCAAs accelerate ammonia detoxification in the brain.