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| BIOCHEMISTRY AND PHARMACOLOGY OF LIPID ANTIOXIDANTS IN ACUTE BRAIN AND SPINAL-CORD INJURY |
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| Author(s): HALL ED, YONKERS PA, ANDRUS PK, COX JW, ANDERSON DK |
| Source: JOURNAL OF NEUROTRAUMA Volume: 9 Pages: S425-S442 Supplement: Suppl. 2 Published: MAY 1992 |
| Times Cited: 81 References: 50 |
| Abstract: Oxygen radical-mediated lipid peroxidation (LP) has been suggested increasingly to be an important factor in posttraumatic neuronal degeneration. Thus, numerous studies have evaluated the neuroprotective efficacy of pharmacological agents with lipid antioxidant activity in models of spinal cord and brain injury. Intensive pretreatment of animals with the endogenous lipid peroxyl radical scavenger vitamin E (i.e., alpha-tocopherol) has been shown to decrease posttraumatic spinal cord ischemia and to enhance chronic neurological recovery. However, the slow CNS tissue uptake of vitamin E requires chronic dosing, making it an impractical agent for treatment of acute neural-injury. The glucocorticoid steroid, methylprednisolone (MP), has been shown to possess significant antioxidant efficacy and, when administered to animals or humans in antioxidant doses, improves chronic neurological recovery after spinal cord injury. This activity of MP is independent of the steroid's glucocorticoid receptor-mediated actions, as evidenced by the efficacy of the novel antioxidant 21-aminosteroids, which are devoid of glucocorticoid activity but have greater antioxidant efficacy than MP. One of these, tirilazad mesylate (U-74006F), has been shown to be effective in animal models of brain and spinal cord injury and is currently the subject of phase II clinical trials. Recently, compounds that combine the amino functionality of the 21-aminosteroids with the peroxyl radical scavenging chromanol portion of vitamin E (i.e., 2-methylaminochromans) also have shown promise as neuroprotective agents. The consistent benefit afforded by antioxidant compounds further supports the concept that LP is an important therapeutic target for acute pharmacological neuroprotection. |
| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: HALL, ED (reprint author), UPJOHN CO, CENT NERVOUS SYST DIS RES, KALAMAZOO, MI 49001 USA |
Addresses:
1. UPJOHN CO, DRUG METAB RES, KALAMAZOO, MI 49001 USA
2. VET ADM MED CTR, CINCINNATI, OH 45220 USA |
| Publisher: MARY ANN LIEBERT INC PUBL, 2 MADISON AVENUE, LARCHMONT, NY 10538 |
| Subject Category: Critical Care Medicine; Clinical Neurology; Neurosciences |
| IDS Number: HU819 |
| ISSN: 0897-7151 |
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