Neuron-specific mitochondrial degeneration induced by hyperammonemia and octanoic acidemia.

The neuropathological consequences of acute exposure to the neurotoxicants ammonia and octanoic acid were investigated with the isolated, perfused canine brain preparation. After 1 h of combined hyperammonemia and octanoic acidemia, ultrastructural changes were apparent in all brain regions examined. The cell bodies of neurons were the primary sites of these alterations. Neuronal mitochondria were distended, and the lamellae of the mitochondrial cristae were separated. In some cases the lamellae had completely dispersed, leaving only matrix remnants. Mitochondria of adjacent astrocytes appeared normal. Thus, a characteristic population of brain mitochondria is selectively vulnerable to a combination of hyperammonemia and octanoic acidemia and may be related to the biochemical mechanisms underlying encephalopathies of hepatic origin.