The role of erythropoietin in central and peripheral nerve injury.

Erythropoietin (Epo) is a cytokine which controls red cell production. Apart from the red cell surface, erythropoietin's receptor (Epo-R) is also expressed in a large variety of normal tissues. Erythropoietin, as well as its receptor, is present in the central and peripheral nervous system. As erythropoietin having direct and indirect effect on nerve cells, enhances antioxidotic enzyme production, antagonizes glutamate's cytotoxic action, metabolizes free radicals, normalizes cerebral blood flow, affects neurotransmitters release and stimulates neoangiogenesis. After injury of the central as well as the peripheral nervous system, Epo presents an anti-apoptotic action. In combination with its anti-apoptotic effect, Epo, by reducing the inflammatory response plays a crucial role in neuroprotection in many types of injury in the central and the peripheral nervous system. Epo's administration contributes to the recovery of mechanical allodynia and may be effective in peripheral nerve regeneration after neurorrhaphy.

Axonal regeneration stimulated by erythropoietin: an experimental study in rats.

The aim of the present study is to evaluate the effects of erythropoietin to the collateral sprouting by using systemically delivered erythropoietin in an end-to-side nerve repair model. Forty-five rats were evaluated in four groups: (A) end-to-side neurorrhaphy only, (B) end-to-side neurorrhaphy and erythropoietin administration, (C) end-to-end neurorrhaphy and (D) nerve stumps buried into neighboring muscles. In all animals, the contralateral healthy side served as control. Functional assessment of nerve regeneration was performed at intervals up to 5 months using the Peroneal Function Index. Evaluation 150 days after surgery included peroneal and tibial nerve morphometric examination, and wet weights of the tibialis anterior muscle. During the first three weeks after surgery, when erythropoietin was regularly administered, functional evaluation showed that erythropoietin may facilitate peripheral nerve regeneration. However, there was rapid deterioration in the functional recovery when erythropoietin's administration was discontinued. As a consequence, at the end of this study, erythropoietin failed to maintain its initial stimulating effect in axonal regeneration. The results of wet muscle weights revealed statistically significant differences between Groups A and C, and Group B. Furthermore, data on axonal counting showed significant difference between Groups A and C, and Group B. Erythropoietin appears to facilitate peripheral nerve regeneration at the initial phase of its administration. Further investigation will be necessary to optimise the conditions (dose, mode of administration) in order to maintain its effects.