title: Posttraumatic epilepsy: hemorrhage, free radicals and the molecular regulation of glutamate.
abstract: Traumatic brain injury causes development of posttraumatic epilepsy. Bleeding within neuropil is followed by hemolysis and deposition of hemoglobin in neocortex. Iron from hemoglobin and transferring is deposited in brains of patients with posttraumatic epilepsy. Iron compounds form reactive free radical oxidants. Microinjection of ferric ions into rodent brain results in chronic recurrent seizures and liberation of glutamate into the neuropil, as is observed in humans with epilepsy. Termination of synaptic effects of glutamate is by removal via transporter proteins. EAAC-1 is within neurons while GLT-1 and GLAST are confined to glia. Persistent down regulation of GLAST production is present in hippocampal regions in chronic seizure models. Down regulation of GLAST may be fundamental to a sequence of free radical reactions initiated by brain injury with hemorrhage. Administration of antioxidants to animals causes interruption of the sequence of brain injury responses induced by hemorrhage, suggesting that such a strategy needs to be evaluated in patients with traumatic brain injury.
authors.affiliation: Department of Neurology & Psychiatry, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MI 63104, USA. willmore@slu.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Willmore
authors.forename: Yuto
authors.initials: Y
authors.lastname: Ueda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D005609:Free Radicals / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000378:metabolism*; D019581:Neuropil / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D050491:Glutamate Plasma Membrane Transport Proteins; D009569:Nitric Oxide; D018698:Glutamic Acid
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