Background: Erythropoietin (Epo) and vascular endothelial growth factor (VEGF) are two vasoactive
molecules with essential trophic effects for brain development. The expression and secretion of both molecules
increase in response to neuronal damage and they exert protective and restorative effects, which may also be
accompanied by adverse side effects.
Objective: We review the most relevant evidence on the neuroprotective and neurorestorative effects of Epo and
VEGF in three of the most frequent neurological disorders, namely, stroke, epilepsy and Alzheimer's disease, to
develop new therapeutic approaches.
Methods: Several original scientific manuscripts and reviews that have discussed the evidence in critical way,
considering both the beneficial and adverse effects of Epo and VEGF in the selected neurological disorders, were
analysed. In addition, throughout this review, we propose several considerations to take into account in the design
of therapeutic approaches based on Epo and VEGF signalling.
Results: Although the three selected disorders are triggered by different mechanisms, they evolve through similar
processes: excitotoxicity, oxidative stress, neuroinflammation, neuronal death, glial reactivity and vascular remodelling.
Epo and VEGF exert neuroprotective and neurorestorative effects by acting on these processes due to
their pleiotropism. In general, the evidence shows that both Epo and VEGF reduce neuronal death but that at the
vascular level, their effects are contradictory.
Conclusion: Because the Epo and VEGF signalling pathways are connected in several ways, we conclude that
more experimental studies, primarily studies designed to thoroughly assess the functional interactions between
Epo and VEGF in the brain under both physiological and pathophysiological conditions, are needed.