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Posttraumatic Epilepsy: Hemorrhage, Free Radicals and the Molecular Regulation of Glutamate

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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.

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Authors and Affiliations

  1. Department of Neurology & Psychiatry, Saint Louis University School of Medicine, 1402 South Grand Blvd. [M226], St. Louis, MI, 63104, USA

    L. J. Willmore

  2. Department of Psychiatry, Miyazaki Medical College, Miyazaki, Japan

    Yuto Ueda

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  1. L. J. Willmore
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  2. Yuto Ueda
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Correspondence to L. J. Willmore.

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Special issue article in honor of Dr. Akitane Mori.

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Willmore, L.J., Ueda, Y. Posttraumatic Epilepsy: Hemorrhage, Free Radicals and the Molecular Regulation of Glutamate. Neurochem Res 34, 688–697 (2009). https://doi.org/10.1007/s11064-008-9841-3

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  • DOI: https://doi.org/10.1007/s11064-008-9841-3

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