METHYLPREDNISOLONE AND MEMBRANE-PROPERTIES OF PRIMARY CULTURES OF MOUSE SPINAL-CORD

The present study attempts to define the capacity of methylprednisolone sodium succinate (MP) to protect neuronal membranes against a free radical challenge in primary cultures of fetal mouse spinal cord. Incubation of these cultures with MP significantly increased the Na+,K+-ATPase activity, an effect that was blocked by the RNA synthesis inhibitor, actinomyosin D and the protein synthesis inhibitor, cycloheximide, suggesting an induction of protein synthesis by MP. In contrast, incubation with FeCl2 for 1 or 2 h significantly inhibited Na+,K+-ATPase activity and elevated the levels of thiobarbituric acid-reactive substances (TBARS). Pretreatment with MP prevented the rise in TBARS and partially prevented the decrease in Na+,K+- ATPase activity for the first hour of FeCl2 incubation, an effect that was lost during the second hour. A second dose of MP after the first hour of incubation with FeCl2 partially restored Na+,K+-ATPase activity and reduced TBARS levels after the second hour of exposure to FeCl2. Co-incubation of MP with cycloheximide completely prevented the decrease in Na+,K+-ATPase activity seen after a 2-h incubation with FeCl2 and eliminated the need for a second dose of MP after the first hour of incubation with FeCl2. These findings suggest a capacity for rapid protein induction and antioxidant activity for MP in vitro.