Amalia Merelli, Liliana Czornyj and Alberto Lazarowski Pages 6791 - 6801 ( 11 )
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.
Cerebral hypoxia, neurodegenration, refractory epilepsy, erythropoietin, HIF-1, P-Glycoprotein
Instituto de Investigaciones en Fisiopatología y Bioquímica Clínica (INFIBIOC), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Junín 956, C1121ABGBuenos Aires, Argentina