title: Postconditioning by mild hypoxic exposures reduces rat brain injury caused by severe hypoxia.
abstract: A potent neuroprotective effect of ischemic postconditioning has previously been described using cerebral artery occlusion but this is not a practical therapeutic option. The present study has been performed to determine whether postconditioning by mild episodes of hypobaric hypoxia (hypoxic postconditioning, HP) can reduce post-hypoxic brain injury in rats. Male Wistar rats were submitted to severe hypobaric hypoxia (180 Torr, 3 h) followed by HP (360 Torr, 2 h, 3 trials spaced at 24 h) starting either 3h (early HP) or 24 h (delayed HP) after severe hypoxia. The structural and functional brain injury was assessed by a complex of histological techniques, behavioral methods, and by testing the functions of the hypothalamic-pituitary-adrenal axis (HPA). It was found that early and delayed HP considerably attenuated post-hypoxic injury, reducing pyknosis, hyperchromatosis, and interstitial brain edema, as well as the rates of neuronal loss in hippocampus and neocortex. Delayed HP produced prominent anxiolytic effect on rat behavior, preventing development of post-hypoxic anxiety. Both modes of HP had beneficial effect on the functioning of HPA, but only delayed HP normalized completely the baseline HPA activity and its reactivity to stress. The results obtained demonstrate that postconditioning by using repetitive episodes of mild hypobaric hypoxia may provide a powerful neuroprotective procedure that can be easily adopted for clinical practice and recommended as a research tool for identification of endogenous mechanisms involved in post-ischemic neuroprotection.
authors.affiliation: Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova 6, 199034 St. Petersburg, Russian Federation. rybnikova1@rambler.ru
authors.forename: Elena
authors.initials: E
authors.lastname: Rybnikova
authors.forename: Maksim
authors.initials: M
authors.lastname: Vorobyev
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pivina
authors.forename: Mikhail
authors.initials: M
authors.lastname: Samoilov
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology; D020208:Brain Injury, Chronic / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D002470:Cell Survival / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003627:Data Interpretation, Statistical; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006728:Hormones / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D002534:Hypoxia, Brain / Q000473:pathology* / Q000628:therapy*; D007091:Image Processing, Computer-Assisted; D019194:Ischemic Preconditioning; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D019579:Neocortex / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006728:Hormones; D003345:Corticosterone