title: Induction of tolerance to ischemia: alterations in second-messenger systems in the gerbil hippocampus.
abstract: Preconditioning the brain with sublethal ischemia protects against neuronal damage following subsequent ischemic insult. Using [3H]inositol 1,4,5-triphosphate (IP3), [3H]phorbol 12,13-dibutyrate (PDBu), [3H]cyclic adenosine monophosphate (cAMP) and [3H]rolipram, we performed quantitative autoradiography to determine postischemic alterations in second-messenger systems in the gerbil hippocampus following preconditioning the brain with sublethal ischemia. At 7 days of reperfusion, no alterations were observed in brains subjected to 2 min of forebrain ischemia which produced no neuronal damage. However, 3-min ischemia caused a 75% reduction in [3H]IP3 binding (p < 0.01 vs. control) and 15-25% reductions in [3H]forskolin (p < 0.01 vs. control), [3H]cAMP (p < 0.05 vs. control), and [3H]rolipram (p < 0.01 vs. control) binding in the CA1 subfield coincident with histopathological CA1 pyramidal cell destruction, but no significant alterations in [3H]PDBu binding. Preconditioning the brain with 2 min of ischemia followed by 4 days of reperfusion prevented both histopathological cell death and the reductions in binding following subsequent 3 min of ischemia. Interestingly, [3H]IP3 and [3H]rolipram binding in CA1 showed a transient reduction, by 30% and 20% (both p < 0.01 vs. control), respectively, in the early reperfusion period. This downregulation of the IP3 system may play a role in the protection against cell death.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Murase
authors.forename: K
authors.initials: K
authors.lastname: Kogure
mesh_terms: D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000503:physiopathology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000502:physiology*; D007293:Inosine Triphosphate / Q000494:pharmacology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D015290:Second Messenger Systems / Q000502:physiology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D007293:Inosine Triphosphate; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D011494:Protein Kinases; D020889:Rolipram