Enhanced erythropoietin expression in the brainstem of newborn rats at high altitude

In addition to its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions against acute and delayed degenerative diseases of the brain. Moreover, we have recently demonstrated that endogenously synthesized Epo and soluble Epo receptor (a negative regulator of Epo binding to the Epo receptor) in the central nervous system play a crucial role in facilitating the ventilatory response and acclimatization to hypoxia. Here we hypothesized that cerebral Epo in the brainstem is implicated in the process that allows cardiorespiratory acclimatization to high altitude hypoxia during the postnatal period. Thus, we evaluated the postnatal ontogeny of cerebral Epo concentration of Sprague-Dawley rats living and reproducing at high altitude for longer than 19 years (3600 m in La Paz, Bolivia). Our results show that postnatal Epo concentration in high-altitude rats is higher in the brainstem than in the forebrain. Moreover, although Epo concentration in the forebrain of high-altitude rats is similar to sea-level controls, Epo level in the brainstem is surprisingly 2-fold higher in high-altitude rats than in sea-level controls. These findings strongly suggest that brainstem Epo plays an important role in tolerance to high altitude hypoxia after birth. From a clinical perspective, a better understanding of the role of Epo in the postnatal development of cardiorespiratory responses in neonates exposed to acute or chronic hypoxia might be useful.

► Epo as a player in the maturation of brainstem respiratory centers.
► Rats living at high altitude as a model of chronic hypoxia in mammals.
► Brainstem shows higher Epo expression than forebrain in postnatal high altitude rats.
► Newborn rats have higher brainstem Epo level at high altitude than at sea level.
► Brainstem Epo is involved in tolerance of high altitude hypoxia from birth.