Title:EPO and EPO-Receptor System as Potential Actionable Mechanism for the Protection of Brain and Heart in Refractory Epilepsy and SUDEP
VOLUME: 26 ISSUE: 12
Author(s):Jerónimo Auzmendi , María B. Puchulu, Julio C. G. Rodríguez , Ana M. Balaszczuk , Alberto Lazarowski and Amalia Merelli *
Affiliation:Universidad de Buenos Aire (UBA), Facultad de Farmacia y Bioquimica (FFyB), Instituto de Fisiopatologia y Bioquimica Clínica (INFIBIOC), Junín 956, Ciudad Autonoma de Buenos Aires (CABA), Buenos Aires, Universidad de Buenos Aires, Facultad de Farmacia y Bioquimica, Departamento de Ciencias Biologicas, Catedra de Fisiologia, Instituto de Quimica y Metabolismo del Farmaco, CONICET, Ciudad Autonoma de Buenos Aires, Buenos Aires, CENPALAB, Centro Nacional para la Producción de Animales de Laboratorio, La Habana, Universidad de Buenos Aires, Facultad de Farmacia y Bioquimica, Departamento de Ciencias Biologicas, Catedra de Fisiologia, Instituto de Quimica y Metabolismo del Farmaco, CONICET, Ciudad Autonoma de Buenos Aires, Buenos Aires, Universidad de Buenos Aire (UBA), Facultad de Farmacia y Bioquimica (FFyB), Instituto de Fisiopatologia y Bioquimica Clínica (INFIBIOC), Junín 956, Ciudad Autonoma de Buenos Aires (CABA), Buenos Aires, Universidad de Buenos Aire (UBA), Facultad de Farmacia y Bioquimica (FFyB), Instituto de Fisiopatologia y Bioquimica Clínica (INFIBIOC), Junín 956, Ciudad Autonoma de Buenos Aires (CABA), Buenos Aires
Keywords:Epilepsy, erythropoietin, erythropoietin receptor, P-glycoprotein, SUDEP, neuroprotection, cardioprotection.
Abstract:The most important activity of erythropoietin (EPO) is the regulation of erythrocyte production by
activation of the erythropoietin receptor (EPO-R), which triggers the activation of anti-apoptotic and proliferative
responses of erythroid progenitor cells. Additionally, to erythropoietic EPO activity, an antiapoptotic effect has
been described in a wide spectrum of tissues. EPO low levels are found in the central nervous system (CNS),
while EPO-R is expressed in most CNS cell types. In spite of EPO-R high levels expressed during the hypoxicischemic
brain, insufficient production of endogenous cerebral EPO could be the cause of determined circuit
alterations that lead to the loss of specific neuronal populations. In the heart, high EPO-R expression in cardiac
progenitor cells appears to contribute to myocardial regeneration under EPO stimulation. Several lines of evidence
have linked EPO to an antiapoptotic role in CNS and in heart tissue. In this review, an antiapoptotic role of
EPO/EPO-R system in both brain and heart under hypoxic conditions, such as epilepsy and sudden death
(SUDEP) has been resumed. Additionally, their protective effects could be a new field of research and a novel
therapeutic strategy for the early treatment of these conditions and avoid SUDEP.
