title: The effects of glucocorticoid and nonglucocorticoid steroids on acute neuronal degeneration.
abstract: The glucocorticoid steroid methylprednisolone (MP) has been shown to enhance chronic recovery after human spinal cord injury when administered in a 24-hr high-dose regimen beginning within 8 hr. The doses of MP that effect this improved recovery have been demonstrated to inhibit spinal tissue LP, which has been postulated to be a key event in the secondary posttraumatic degenerative cascade. The molecular mechanism of action of the steroid appears to involve intercalation into the cell membrane and blockade of the propagation of LP reactions. At a physiological level, the inhibition of injury-induced LP has been found to result in an attenuation of progressive posttraumatic ischemia and energy failure together with an augmented reversal of intracellular calcium accumulation. However, MP also acts directly to retard secondary neuronal degeneration, as observed in studies showing the steroid's ability to slow the anterograde degeneration of experimentally injured cat soleus motor nerves. The duplication of this effect by the nonsteroidal lipid antioxidant alpha-tocopherol supports the notion that it is indeed a manifestation of the inhibition of posttraumatic LP. Moreover, the efficacy of MP in limiting lipid peroxidation and secondary spinal cord or motor nerve degeneration has also been duplicated by a nonglucocorticoid 21-aminosteroid, tirilazad mesylate (U-74006F), which suggests the independence of the antioxidant and glucocorticoid effects of MP.
authors.affiliation: Central Nervous System Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: E D
authors.initials: ED
authors.lastname: Hall
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013256:Steroids / Q000494:pharmacology*
chemical_list: D005938:Glucocorticoids; D013256:Steroids