Impact acceleration-induced severe diffuse axonal injury in rats: characterization of phosphate metabolism and neurologic outcome.

Diffuse axonal injury (DAI) occurs in over half of all severe cases of traumatic brain injury and has been associated with the development of a persistent vegetative state. Although a number of studies have examined the biochemical and physiological events following brain trauma, none of these has concentrated on events associated with the occurrence of severe DAI. The present study has used phosphorus magnetic resonance spectroscopy (MRS) and the rotarod motor test to characterize metabolic and neurologic consequences of severe diffuse axonal injury in rats induced by impact acceleration. Traumatic brain injury was induced in male rats by dropping a 450-g brass weight a distance of 2 m onto a 10-mm stainless-steel disc (3 mm wide) attached to the closed skull. Changes in brain intracellular pH, free magnesium concentration, cytosolic phosphorylation ratio, and mitochondrial oxidative metabolism after injury were monitored by phosphorus MRS while neurologic motor outcome over 1 week was assessed using the rotarod test. Impact acceleration-induced injury resulted in a highly significant decline in free magnesium concentration, cytosolic phosphorylation ratio, and an increased rate of mitochondrial oxidative phosphorylation, but no significant change in pH. These changes were associated with the occurrence of a significant neurologic deficit over 1 week postinjury. The similarity in metabolic events associated with production of neurologic deficits in this and other models of traumatic brain injury suggests that these bioenergetic changes may be common to all models of brain trauma.