title: Glucocorticoid mechanisms in acute spinal cord injury: a review and therapeutic rationale.
abstract: This review seeks to provide pharmacological evidence that intensive glucocorticoid dosing can enhance sensorimotor recovery after blunt spinal cord trauma. It is suggested that high doses of glucocorticoids can beneficially affect the injured cord through the influence of at least three mechanisms. These are: (1) a facilitation of neuronal excitability and impulse conduction; (2) an improved blood flow; and, perhaps most importantly, (3) the preservation of cord ultrastructure through a reduction of injury-induced, free radical--catalyzed lipid peroxidation. In the case of methylprednisolone, the minimal intravenous dosage required to initially achieve each of these effects is in the range of 15 to 30 mg per kilogram of body weight, which is beyond that used currently for neurosurgical purposes. In addition, based upon the hypothesized mechanism of action and the tissue pharmacokinetics, the earliest possible initiation of therapy is imperative and rigorous maintenance dosing for an as yet undetermined length of time is needed.
mesh_terms: D000208:Acute Disease; D001696:Biomechanical Phenomena; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D009410:Nerve Degeneration; D012039:Regional Blood Flow; D012306:Risk; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D008054:Lipid Peroxides