REMOTE ISCHEMIC PRE- AND POSTCONDITIONING ABOLISHED DELAYED HIF-1a EXPRESSION IN THE RAT HIPPOCAMPUS ALONGSIDE WITH THE CORRECTION OF EXPERIMENTAL POST-TRAUMATIC STRESS DISORDER

Aims of the study. To examine effects of remote ischemic pre- and postconditioning which prevents development of the experimental post-traumatic s tress disorder (PTSD) in rats on the dynamics of expression of regulatory a-subunit of hypoxia-inducible factor (HIF-1a) in hippocampus. Materials and methods. Using immunohistochemistry method, the level of HIF-1a immunoreactivity has been quantitatively assessed in the hippocampus of animals exposed to stressors in the “traumatic stress-restress” paradigm, and by using the three-time remote limb ischemia which prevented the formation of anxiety pathology in this model. Results. Development of the PTSD-like pathology in rats was accompanied by considerable and persistent (up to 10 days after restress) up-regulation of HIF-1a immunoreactivity level in the CA1 field and dentate gyrus of hippocampus. Conditioning remote ischemia applied before traumatic stress (preconditioning) or following restress (postconditioning) did not affect early post-stress induction of HIF-1a (the first day) but abolished the delayed overexpression of this factor (5-10 days). Conclusions. The data obtained support our recent hypothesis on the pathogenic role of increased HIF-1 factor activity for the development of stress-related anxiety and depressive disorders within the delayed time-period. This also gives evidence to the fact that normalization of delayed violations of HIF-1a expression is obviously the key link of stress-protective effects of remote ischemic conditioning.

HIF-1a, HIF-1a, post-traumatic stress disorder, PTSD, remote ischemic preconditioning and postconditioning, anxiolytic effect, stress-protective action