Effect of phenytoin and corticosteroids on seizures and lipid peroxidation in experimental posttraumatic epilepsy.
Head trauma, intracerebral hematoma formation, and hemorrhagic cerebral infarction cause extravasation of the intravascular contents, red blood cell (RBC) hemolysis, hemosiderin deposition within the neuropil, and an increased incidence of epilepsy. Reports conflict regarding the efficacy of the administration of prophylactic anticonvulsant drugs to head-injured patients to prevent the development of posttraumatic epilepsy. In this study, rats received a 10-microliter injection of 100 mM FeCl2 at a depth of 1.8 mm into the isocortex, or an equal volume of saline. Rats were then treated with 30 mg/kg methylprednisolone (MPS), 90 mg/kg MPS, 100 mg/kg phenytoin, or with an equal volume of propylene glycol. Behavioral or electroencephalographic (EEG) seizures occurred in all control-treated iron-injected rats within 93 +/- 6 minutes of injection. Brain injury responses as measured by the occurrence of fluorescent product formation from iron-induced lipid peroxidation showed 6.6 +/- 0.8 units/gm in the saline-injected animals, and 16.7 +/- 2.5 units/gm in the control-treated iron-injected rats. Of the 90-mg/kg MPS-treated rats, 8% had seizures; fluorescence in those animals was 5.7 +/- 0.5 units/gm. Phenytoin treatment prevented the occurrence of convulsive and EEG seizures; however, lipid peroxidation was unaffected (16.5 +/- 4.1 units/gm). If posttraumatic epilepsy develops because of RBC extravasation, hemolysis, parenchymal deposition of heme compounds, and initiation of lipid peroxidation, then treatments designed to prevent peroxidation may be more effective for epilepsy prophylaxis than administration of anticonvulsant drugs that mask convulsive seizures while biochemical brain injury continues.
D000818:Animals; D001930:Brain Injuries / Q000150:complications; D002712:Chlorides; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005290:Ferric Compounds; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D010672:Phenytoin / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D005290:Ferric Compounds; D008054:Lipid Peroxides; D010672:Phenytoin; C024555:ferric chloride; D008775:Methylprednisolone