Effects of methylprednisolone on axonal depression induced by hypoxia, gamma-aminobutyric acid, and (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide.

Abstract

We sought to confirm the effects of methylprednisolone (MP) on axonal depression induced by hypoxia, gamma-aminobutyric acid (GABA), and (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT). Compound action potentials were recorded to assess the effects of MP in neonatal rat spinal cord axons. Longitudinally hemisected spinal cords were superfused for 120 minutes in Ringer's solution saturated with 95% N2 and 5% CO2. The effect of MP on GABA- and 8-OH-DPAT-induced axonal depression was analyzed with oxygenated isolated dorsal columns. Hypoxia (120 min) significantly reduced the response amplitudes in hemicord preparations. MP (30 micromol/L) prevented hypoxia-induced depression of action potential amplitudes. In oxygenated dorsal column preparations, GABA (50 micromol/L) significantly reduced action potential amplitudes. At 10, 30, and 100 micromol/L, MP had no effect on axonal excitability and GABA-induced axonal depression. 8-OH-DPAT (100 micromol/L) significantly reduced the action potential amplitude. MP (10, 30, 50, and 100 micromol/L) reduced 8-OH-DPAT-induced amplitude depression in a dose-dependent manner. At the higher concentrations, MP protected spinal cord axons against hypoxia-induced excitability loss. It had an effect on serotonin 1A-induced axonal depression but not on GABA-induced depression.