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Epilepsy Behav. 2005 Dec;7 Suppl 3:S12-7. Epub 2005 Oct 18.

Interventions with neuroprotective agents: novel targets and opportunities.

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Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.


Several antiepileptic drugs have demonstrated neuroprotective properties in animal models by inhibiting the components of the excitotoxic cascade. The process of neurodegeneration appears to be dependent on the mitochondria, with their central role as regulators of both energy metabolism and apoptotic pathways during seizures. Excess cytosolic Ca(2+) during periods of excitotoxicity disrupts homeostasis in the mitochondria, causing inhibition of adenosine triphosphate synthesis and increased production of reactive oxygen species, with resultant oxidative damage, leading to neuronal cell death. The Ca(2+)-mediated mitochondrial dysfunction in epilepsy may be the main target for neuroprotective intervention by antiepileptic drugs.

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