Mutually protective actions of kainic acid epileptic preconditioning and sublethal global ischemia on hippocampal neuronal death: involvement of adenosine A1 receptors and K(ATP) channels.
Preconditioning with sublethal ischemia attenuates the detrimental effects of subsequent prolonged ischemic insults. This research elucidates potential in vivo cross-tolerance between different neuronal death-generating treatments such as kainate administration, which induces seizures and global ischemia. 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-minute 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 KA before a 7.5-mg/kg KA injection. The interval between treatments was 3 days. Neuronal degeneration, revealed by the silver impregnation method and analysis of cresyl violet staining, was markedly reduced in rats preconditioned with a sublethal ischemia or a 5-mg/kg KA treatment. Labeling with terminal deoxynucleotidyl 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 preconditioned animals. The current study supports the existence of bidirectional cross-tolerance between KA excitotoxicity and global ischemia and suggests the involvement of adenosine A1 receptors and sulfonylurea- and ATP-sensitive K+ channels in this protective phenomenon.
Plamondon
H
H
University of Ottawa, School of Psychology, Ontario, Canada.
Blondeau
N
N
Heurteaux
C
C
Lazdunski
M
M
D000818:Animals; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D018696:Neuroprotective Agents; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D010660:Phenylisopropyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D007608:Kainic Acid; D005905:Glyburide