Protective Effect of Hypothermia on Ammonia Toxicity and Energetic Disturbances in Astrocytes

¹Department of Organic Chemistry, University of Bremen, Bremen, Germany; ²Centre de Recherche, Hospital Saint-Luc, Montreal, Quebec, Canada

Ammonia causes cell swelling and energy failure of astrocytes in hepatic encephalopathy (HE). Since mild hypothermia is known to offer protection from encephalopathy in HE, we investigated if hypothermia protects against ammonia-induced energy failure in cultured astrocytes, the major target in HE. Mild and moderate hypothermia attenuated the depletion of high-energy phosphates and prevented severe lactate accumulation. Mitochondrial glucose flux contributing to glutamine synthesis decreased, while direct conversion of glutamate and ammonia to glutamine was still significantly elevated. The results suggest that hypothermia-induced protection against ammonia toxicity results from reduced energy demands in reactions uncoupled from mitochondrial energy metabolism.