Spinal cord injury and protection.
Subsequent to traumatic injury of the spinal cord, a series of pathophysiological events occurs in the injured tissue that leads to tissue destruction and paraplegia. These include hemorrhagic necrosis, ischemia, edema, inflammation, neuronophagia, loss of Ca2+ from the extracellular space, and loss of K+ from the intracellular space. In addition, there is trauma-initiated lipid peroxidation and hydrolysis in cellular membranes. Both lipid peroxidation and hydrolysis can damage cells directly; hydrolysis also results in the formation of the biologically active prostaglandins and leukotrienes (eicosanoids). The time course of membrane lipid alterations seen in studies of antioxidant interventions suggests that posttraumatic ischemia, edema, inflammation, and ionic fluxes are the result of extensive membrane peroxidative reactions and lipolysis that produce vasoactive and chemotactic eicosanoids. A diverse group of compounds has been shown to be effective in ameliorating spinal cord injury in experimental animals. These include the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS); the antioxidants vitamin E, selenium, and dimethyl sulfoxide (DMSO); the opiate antagonist naloxone; and thyrotropin-releasing hormone (TRH). With the exception of TRH, all of these agents have demonstrable antioxidant and/or anti-lipid-hydrolysis properties. Thus the effectiveness of these substances may lie in their ability to quench membrane peroxidative reactions or to inhibit the release of fatty acids from membrane phospholipids, or both. Whatever the mode of action, early administration appears to be a requirement for maximum effectiveness.
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000032:analysis / Q000378:metabolism*; D002415:Cats; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis; D005609:Free Radicals; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis; D008054:Lipid Peroxides / Q000378:metabolism; D010264:Paraplegia / Q000209:etiology; D013116:Spinal Cord / Q000032:analysis; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D014022:Tissue Survival / Q000187:drug effects
D000975:Antioxidants; D001095:Arachidonic Acids; D005609:Free Radicals; D006888:Hydroxycholesterols; D008054:Lipid Peroxides; D016718:Arachidonic Acid; C007997:25-hydroxycholesterol; D002784:Cholesterol