Metabolic Inhibition and Selective Axonal Injury

Abstract

The selective injury of CNS axons produced by exposure to Cd₂₊, an environmental contaminant, is a result of disruption of mitochondrial respiration (oxidative phosphorylation). An examination of the literature reveals some other poisons that have a similar effect upon oxidative phosphorylation and that also produce CNS lesions typified by damage of axons with selective sparing of neurons. These include cyanide, CO, CS₂, arsenic, and azide. The neurological injuries produced by these toxins appear to constitute a distinct class of pathology in which axonal injury is dominant. Such an observation is paradoxical, considering that ischemia tends to produce selective injury of neurons with relative sparing of axons, the mirror image of the injury associated with disruption of oxidative phosphorylation by these toxins. This paradox may be resolved by considering the extent to which energy utilization is disrupted during these two classes of metabolic insult. It appears likely that low levels of cytochrome oxidase, which is required for oxidative phosphorylation, endow white matter with a relatively high sensitivity to insults that disrupt oxidative phosphorylation.