ERYTHROPOIETIN NEUROPROTECTIVE PROPERTY AS NEW AS THERAPEUTIC TOOL FOR APNEA OF PREMATURITY

Abstract

We tested the hypothesis that Epo (Erythropoietin) protects newborns against the consequences of IH induced by apnea of prematurity (AoP). As caffeine (despite ineffective in about 50% of cases) is the treatment of choice of AoP, the effect of Epo and caffeine was compared.Male and female newborn rats exposed to IH during postnatal days (P) 3–10 were used in this work. During this time, animals were daily gavage with vehicle, Epo, caffeine, and Epo+caffeine (10–12 pups/group). At P10 the frequency of apneas and mean duration of apnea at rest were measured (as index of respiratory dysfunction induced by IH) plethysmography. Next, the hippocampus, cortex, and brainstem were harvested, and the activity of Superoxide‐Dismutase (SOD – major anti‐oxidant), Glutathion peroxydase (GPx) and NADPH oxidase (NOX – major pro‐oxidant) enzymes were evaluated.Our results showed that IH increased the frequency of apnea and mean duration of apnea in male and female, reduced SOD anf GPx activity, but increased NOX activity. Interestingly, Epo and caffeine significantly reduced apnea frequency, but only Epo efficiently restored the oxidant activity to normal levels. Moreover, the administration of Epo and caffeine together provided cumulative beneficial effects in reducing the apneic episodes in male and female pups.We conclude that Epo and caffeine activate different, but complementary mechanisms to decrease apneas, suggesting that combined Epo+caffeine treatment could be clinically relevant against AoP.Support or Funding InformationFounded by CIHR, Région Rhône alpes and consulat de France à Québec.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.