title: Interventions with neuroprotective agents: novel targets and opportunities.
abstract: 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.
authors.affiliation: Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA. PatSull@uky.edu
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D004827:Epilepsy / Q000178:diet therapy; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D000927:Anticonvulsants; D002352:Carrier Proteins; D004041:Dietary Fats; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D002118:Calcium