Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage

A new field of clinical and scientific interest has recently developed based on the discovery that the hematopoietic cytokine erythropoietin (Epo) has important non-hematopoietic functions in the brain and other organs, particularly during development. The biological effects of Epo in the central nervous system (CNS) involve activation of its specific receptor and corresponding signal transduction pathways. Epo receptor expression is abundant in the developing mammalian brain, and decreases as term approaches. Epo has been identified as a neurotrophic and neuroprotective agent in a wide variety of experimental paradigms, from neuronal cell culture to in vivo models of brain injury. Several mechanisms by which Epo produces neuroprotection are recognized. Epo (i) decreases glutamate toxicity, (ii) induces the generation of neuronal anti-apoptotic factors, (iii) reduces inflammation, (iv) decreases nitric oxide-mediated injury, and (v) has direct antioxidant effects. Conclusion: Collectively, the evidence suggests that Epo may provide a new approach to the treatment of a variety of CNS disorders in adults and children, especially as a possible therapy for perinatal asphyxia. This review summarizes the current knowledge on the neurotrophic and neuroprotective functions of Epo in the developing and injured brain.