title: Implications for neuroprotective treatments.
abstract: Pharmacological neuroprotection against the consequences of seizures can be considered as primary neuroprotection where the object is to diminish the initial insult by suppressing the seizure activity or diminishing the associated ionic fluxes (of which the entry of Na+ and Ca2+ are the most significant), and secondary neuroprotection where the target is some later event in the chain linking ionic changes to altered brain morphology or function. Thus primary neuroprotection is provided by antiepileptic drugs and compounds acting on voltage-sensitive Na+ and Ca2+ channels or on glutamate receptors (NMDA, AMPA/KA or Group I metabotropic). Secondary neuroprotection may be a result of acting on the cascade leading to necrosis (e.g. free radical scavengers, NitricOxide synthase inhibitors, CycloOxygenase-2 inhibitors) or the cascades leading to apoptosis (e.g. MAP-kinase inhibitors, caspase-3 inhibitors). Other approaches may diminish the long-term morphological and functional effects of seizures (e.g. neurotrophin-related therapies). We need improved preclinical tests for identifying novel compounds with potential for providing secondary neuroprotection and antiepileptogenesis. Clinical trials of neuroprotective agents in chronic epilepsy in adults pose major practical difficulties but the severe childhood epilepsies provide opportunities for aggressive testing of novel compounds.
authors.affiliation: GKT School of Biomedical Sciences, Henriette Raphael House, Guy's Campus, London SE1 1UL, UK. brian.meldrum@kcl.ac.uk
authors.forename: Brian S
authors.initials: BS
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D018696:Neuroprotective Agents / Q000145:classification / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D018696:Neuroprotective Agents