Title:Erythropoietin: A Neuroprotective Agent in Cerebral Hypoxia, Neurodegeneration, and Epilepsy
Volume: 19
Issue: 38
Author(s): Amalia Merelli, Liliana Czornyj and Alberto Lazarowski
Affiliation:
Keywords:
Cerebral hypoxia, neurodegenration, refractory epilepsy, erythropoietin, HIF-1, P-Glycoprotein
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.