title: Erythropoietin: a neuroprotective agent in cerebral hypoxia, neurodegeneration, and epilepsy.
abstract: Neuronal damage secondary to brain injuries such as cerebral hypoxia, seizures as well as neurodegenerative process, may include pro-inflammatory changes. The activation of a common mechanism related to survival or cell death, mediated by the stabilization and trans-activation of Hypoxia-Inducible Factor 1 (HIF-1), has been observed in these conditions. HIF-1 may induce over expression of P-glycoprotein, the product multidrug-resistance gene (MDR-1), both on blood-brain barrier as well as on the cerebral damaged cells, producing the refractoriness to therapeutic strategies for neuroprotection. However, in these same cells, HIF-1 can also induce the expression of erythropoietin receptor (Epo-R). Irrespective of its known properties on hematopoiesis, it was proposed that erythropoietin can trigger neuroprotective mechanisms mediated by Epo-R activation. Brain hypoxia, epilepsy, neurodegeneration and inflammation, can share the induction of Epo-R and several other growth factor receptors as well as signal transductions pathways after HIF-1 transactivation. Perhaps, the use of the intranasal route for the exogenous administration of Epo, (or other biological compounds) could help neuroprotection as well as to repair the brain areas damaged.
authors.affiliation: Instituto de Investigaciones en Fisiopatología y Bioquímica Clínica (INFIBIOC), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Junín 956, C1121ABGBuenos Aires, Argentina. alazarowski@gmail.com.
authors.forename: Amalia
authors.initials: A
authors.lastname: Merelli
authors.forename: Liliana
authors.initials: L
authors.lastname: Czornyj
authors.forename: Alberto
authors.initials: A
authors.lastname: Lazarowski
mesh_terms: D000818:Animals; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D004921:Erythropoietin / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000503:physiopathology; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017467:Receptors, Erythropoietin / Q000502:physiology
chemical_list: D051793:Hypoxia-Inducible Factor 1; D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D018698:Glutamic Acid