Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and (Na+ + K+)-ATPase activity

Dose-response analysis during 1st hour after contusion injury in the cat

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  • 1 Program in Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown, Ohio
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✓ The present study was undertaken to examine the ability of a single large intravenous dose of methylprednisolone (15, 30, or 60 mg/kg) to attenuate lipid peroxidation and enhance (Na+ + K+)-ATPase activity during the 1st hour after a 400 gm-cm injury to the cat spinal cord. The contusion injury was associated with a rise in the concentration of fluorescent lipid peroxy products in the injured segment at 1 hour. In addition, the accumulation of cyclic guanosine 3″,5″-monophosphate (cyclic GMP), which was used as a new index of injury-induced free radical reactions, in the injured spinal segment was twice control levels. The injury-induced increase in fluorescence and cyclic GMP content in the contused spinal segment at 1 hour was completely prevented by the administration of 15 or 30 mg/kg of methylprednisolone at 30 minutes after injury. A 60-mg/kg dose, however, did not prevent the elevation in cyclic GMP. A concomitant examination of the acute effects of glucocorticoid administration on (Na+ + K+)-ATPase activity in the injured cord revealed a striking increase of enzyme activity after the 30-mg/kg dose, but a depression in activity with the 60-mg/kg dose. These results demonstrate that a single massive dose of methylprednisolone can beneficially reduce free-radical reactions and lipid peroxidation as well as enhance the activity of neuronal (Na+ + K+)-ATPase during the early phase after spinal cord contusion. The requirement for doses to be in the range of 15 to 30 mg/kg in order to produce these neurochemical changes is consistent with other studies that have demonstrated significantly greater recovery and tissue preservation in spinal cord-injured animals treated with comparable doses of methylprednisolone soon after injury. These findings suggest the need for a rigorous approach to glucocorticoid therapy in central nervous system trauma.

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