Neuroprotective actions of glucocorticoid and nonglucocorticoid steroids in acute neuronal injury.
1. 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 affect this improved recovery have been demonstrated to inhibit posttraumatic spinal cord lipid peroxidation (LP), which has been postulated to be a key event in the secondary injury-induced degenerative cascade. 2. The molecular mechanism of action of the steroid appears to involve intercalation into the cell membrane and blockade of the propagation of peroxidative 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. 3. The duplication of this effect by the nonsteroidal lipid antioxidant alpha-tocopherol supports the notion that 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.
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Upjohn Company, Kalamazoo, Michigan 49001.
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008775:Methylprednisolone / Q000627:therapeutic use*; D009046:Motor Neurons / Q000187:drug effects; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011281:Pregnatrienes / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013256:Steroids / Q000494:pharmacology* / Q000627:therapeutic use
D005938:Glucocorticoids; D008054:Lipid Peroxides; D011281:Pregnatrienes; D013256:Steroids; D008775:Methylprednisolone; C053355:tirilazad