Erythropoietin and its antagonist regulate hypoxic fictive breathing in newborn mice.
Clinical use of erythropoietin in adult and newborn patients has revealed its involvement in neuroprotection, neurogenesis, and angiogenesis. More recently, we showed in adult mouse, that brain erythropoietin interacts with the major brainstem centers associated with respiration to enhance the ventilatory response to acute and chronic conditions of physiological hypoxia (e.g., as occurring at high altitude). However, whether brain erythropoietin is involved in breathing regulation in newborns remains unknown. In this study, en bloc brainstem-spinal cord preparations were obtained from mice at postnatal day 4. After various periods (30, 60, or 90 min) of incubation with 0, 25, or 250 U of erythropoietin, preparations were superfused with artificial cerebrospinal fluid bubbled with normoxic or hypoxic gas mixtures. The electrophysiological fictive breathing produced by axons at the C4 ventral root was next recorded. Our results show that erythropoietin attenuates the hypoxia-mediated decrease of the central respiratory activity and improves post-hypoxic recovery. Additional analysis revealed that the soluble erythropoietin receptor (the endogenous erythropoietin antagonist) dramatically decreases neural hypoxic respiratory activity, confirming the specific erythropoietin effect on respiratory drive. These results imply that erythropoietin exerts main modulation and maintenance of respiratory motor output during hypoxic and post-hypoxic challenges in 4-days old mice.
Départment de Pédiatrie, Centre de Recherche de l'Hôpital St-François d'Assise (CR-SFA), Centre Hospitalier Universitaire de Québec (CHUQ), Faculté de Médecine, Université Laval, Québec, QC, Canada. khemiri.hanan@gmail.com
Hanan
H
Khemiri
Tommy
T
Seaborn
Christian
C
Gestreau
Jorge
J
Soliz
D000531:Altitude; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002555:Cerebrospinal Fluid; D004921:Erythropoietin / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012119:Respiration / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D004921:Erythropoietin