Mutually protective actions of kainic acid epileptic preconditioning and sublethal global ischemia on hippocampal neuronal death: Involvement of adenosine A(1) receptors and K-ATP channels

Preconditioning, with sublethal ischemia attenuates the detrimental effects of subsequent prolonged ischemic insults. This research elucidates potenti al in vivo cross-tolerance between different neuronal death-generating trea tments such as kainate administration, which induces seizures and global is chemia. This study also investigates the effects of a mild epileptic insult on neuronal death in rat hippocampus after a subsequent, lethal epileptic stress using kainic acid (KA) as a model of epilepsy. Three preconditioning groups were as follows: group 1 was injected with 5 mg/kg KA before a 6-mi nute global ischemia; group 2 received a 3-minute global ischemia before 7. 5 mg/kg KA; and group 3 was injected with a 5-mg/kg dose of KG before a 7.5 -mg/kg KA injection. The interval between treatments was 3 days, Neuronal d egeneration, revealed by the silver impregnation method and analysis of cre syl violet staining, was markedly reduced in rats preconditioned with a sub lethal ischemia or a 5-mg/kg KA treatment. Labeling with terminal deoxynucl eotidyl transferase-mediated 2'-deoxyuridine 5'triphosphate-biotin nick-end labeling and DNA laddering confirmed the component of DNA fragmentation in the death of ischemic and epileptic neurons and its reduction in all preco nditioned animals. The current study supports the existence of bidirectiona l cross-tolerance between KA excitotoxicity and global ischemia and suggest s the involvement of adenosine A(1) receptors and sulfonylurea- and ATP-sen sitive K+ channels in this protective phenomenon.