Brain mitochondria as potential therapeutic targets for managing hepatic encephalopathy

Hepatic encephalopathy (HE) is a critical clinical complication. There is a consensus that ammonia plays a pivotal role in the pathogenesis of HE. Ammonia is a neurotoxin which induces a wide range of functional disturbances in the central nervous system (CNS). On the other hand, HE is associated with the increased free radical formation, tissue inflammation, disturbed neurotransmission, astrocytes swelling, brain edema, and brain herniation. In view of the severe CNS complications ensued HE, potential therapeutic points of intervention need to be vigorously investigated. A role for CNS mitochondrial damage and energy crisis has been considered in HE. It has been found that ammonia induces mitochondrial impairment as a result of a multifaceted interaction of different signaling molecules. Hence, ammonia-induced mitochondrial injury and compromised brain energy metabolism might play a vital role in the pathogenesis of ammonia neurotoxicity. This review focuses on the concept that mitochondrial dysfunction and cellular energy crisis indeed plays a critical role in the pathogenesis of hyperammonemia-induced brain injury. Further, it will highlight the potential therapeutic value of mitochondrial protecting agents and energy providers in the management of HE. The data collected in this review might provide clues to new therapeutic interventions aimed at minimizing HE-associated complications.