EN
BACKGROUND AND AIMS: Complications after neonatal asphyxia are the most common cause of subsequent neurological disorders. The mechanism involved in brain damage is closely associated with abnormal iron metabolism that is a cofactor of free-radical reactions. There is a number of evidence that one of the endogenous processes that protect the brain from damage due to perinatal hypoxia is decreasing of body temperature. It is also known, that the transcriptional hypoxia-inducible factor1α (HIF-1α) plays the fundamental role in adaptive process in response to hypoxia. HIF-1α upregulates several genes involved in glycolysis, erythropoiesis, and angiogenesis to promote survival. Our experiments aimed at checking the effects of body temperature during simulated perinatal anoxia on the subsequent changes of HIF-1α expression in brain. Considering the key role of iron as a cofactor of free radical reactions and it’s contribution in proteasomal degradation of α subunit of HIF protein, the second goal of the project was to verify the influence of deferoxamine (iron chelating agent) on the level of expression of HIF-1α in a variety of thermal conditions. METHODS: Two-day-old Wistar rats were divided into 4 temperature groups: (1) hypothermic (31°C), (2) normothermic (33°C), (3) hyperthermic typical to adult rats (37°C) and (4) hyperthermic typical to febrile adults rats (39°C). Within each group, infants were divided into two subgroups: animals with saline injection and animals with deferoxamine injection. The temperature was controlled starting 15 minutes before, and continuing during 10 minutes of anoxia (pure nitrogen atmosphere) as well as for 2 hours postanoxia. Levels of HIF-1α gene expression were analyzed post mortem: immediately, 3 and 7 days after anoxia using Western blot analysis. RESULTS: The results showed, that the body temperature during neonatal anoxia affects the level of HIF-1α expression. Moreover, the use of deferoxamine increases the expression of this gene.