Prophylactic antiepileptic drugs apparently fail to inhibit the process of epileptogenesis. Are there biochemical strategies that could disrupt the brain injury responses associated with the development of epilepsy?

Antiperoxidants may be of value in modulating brain injury responses. The actions of enzymes such as catalase, peroxidase, and superoxide dismutase quench hydroxyl radicals, superoxide radicals, and peroxides generated in biological systems by oxidative chemistry or by the actions of heme-containing compounds liberated within lipid systems.97 Glutathione peroxidase, using glutathione as a co-substrate and selenium as a metallic co-factor, reduces intracellular formation of hydrogen peroxide and free radicals. Oxidative stress increases activity of glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase.98,99 Selenium, a metallic cofactor of glutathione peroxidase, also seems to act synergistically with ƒnalpha-tocopherol in preventing peroxidation of structural membrane components.

Alpha-tocopherol prevents peroxidative injury of sulfhydryl groups of glycolipids and glycoproteins, apparently augmenting the antioxidant effects of enzyme systems such as glutathione peroxidase. Tocopherol also prevents peroxidation of unsaturated fatty acids and lipids by reaction of phenolic hydroxyl groups with propagating lipid radicals that were initiated by oxidative carbonyl hydrogen abstraction.100-103 Furthermore, the phytyl side chain of tocopherol may intercalate within the acyl chains of polyunsaturated phospholipids, causing lipid membrane stabilization and a reduction in membrane permeability.104,105Tocopherol may also act as a free-radical scavenger and singlet oxygen-quenching agent.103 A novel nonglucocorticoid 21Vaminosteroid, with properties of inhibiting iron-dependent lipid peroxidation, had a salutary effect on concussive injury to mice.106,107

Superoxide radicals induce cellular and vasogenic edema.108-110 Initiation of focal edema by cold-induced injury to the cerebral cortex of rodents causes increased levels of superoxide radicals.108 Administration of liposome-entrapped copper-zinc superoxide dismutase interferes with the development of cold-induced edema, suggesting that super- oxide dismutase interruption of oxygen free-radical¡Vinduced fatty acid injury may have the potential for interruption of trauma-induced brain injury.108

Adapted from: Willmore LJ. Head trauma and the development of post-traumatic epilepsy. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;229¡V238.
With permission from Elsevier (www.elsevier.com). 

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Reviewed By: 
Steven C. Schachter, MD
on: 
Thursday, April 1, 2004