title: Brief anoxia preconditioning and HIF prolyl-hydroxylase inhibition enhances neuronal resistance in organotypic hippocampal slices on model of ischemic damage.
abstract: It is well known that a brief anoxia or hypoxia episodes can render brain resistant to a subsequent ischemia. Recent investigations indicate that mechanisms of such stimulated endogenous neuroprotection are related to the family of hypoxia-inducible factors (HIF), however there are still little data available on the role of HIF family members in hippocampus-a brain structure, highly sensitive to oxygen deficiency. We have used the model of cultured hippocampal slices and single-cell quantitative RT-PCR to study HIF-1α and HIF-3α mRNA expression following triple 5-min mild anoxia, 30-min oxygen-glucose deprivation and their combination. We also tested the effects of HIF prolyl-hydroxylase inhibition with 2,4-pyridinedicarboxylic acid diethyl ester pre-treatment followed by a 30-min oxygen-glucose deprivation. It was found that neuronal damage induced by oxygen-glucose deprivation was accompanied by a significant decrease in both HIF-1α and HIF-3α mRNA levels in CA1 but not CA3 neurons. Anoxia preconditioning did not affect cell viability and HIF mRNA levels but applied before oxygen-glucose deprivation prevented neuronal damage and suppression of HIF-1α and HIF-3α mRNA expression. It was also found that effects of the prolyl-hydroxylase inhibitor were similar to anoxia preconditioning. These results suggest that anoxia preconditioning increases anti-ischemic neuronal resistance which to a certain extent correlates with the changes of HIF-1α and HIF-3α expression.
authors.affiliation: Department of Cytology, Bogomoletz Institute of Physiology, National Academy of Sciences, Ukraine.
authors.forename: Iryna
authors.initials: I
authors.lastname: Lushnikova
authors.forename: Maxim
authors.initials: M
authors.lastname: Orlovsky
authors.forename: Victor
authors.initials: V
authors.lastname: Dosenko
authors.forename: Anastasiia
authors.initials: A
authors.lastname: Maistrenko
authors.forename: Galina
authors.initials: G
authors.lastname: Skibo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020520:Brain Infarction / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D019194:Ischemic Preconditioning / Q000379:methods*; D009924:Organ Culture Techniques; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
chemical_list: C497444:Hif1a protein, rat; C424683:Hif3a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D011393:Procollagen-Proline Dioxygenase