Delayed erythropoietin administration promotes neuronal survival and axonal sprouting with an increase in the motor recovery after mild focal cerebral ischaemia in mice

Apart from its hematopoietic and since shortly its neuroprotective role upon ischemia of brain, retina and spinal cord, Erythropoietin (Epo) is a hormone that opens therapeutic possibilities also in the context of neurorehabilitation after stroke.

This study investigated how subacute delivery of Epo, starting at 3 days after stroke onset, and continuing for 30 days (1 I.U./day or 10 I.U./day; via mini osmotic pump), influences neuronal survival, axonal sprouting and neurological function abnormalities in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion.

Epo administered in a 10 I.U./day dose, in contrast to the 1 I.U./day administration, showed significant increase in neuronal survival and CD31 + newly-formed capillaries, preparing in this way the neuro-vascular niche needed for further neuroregeneration processes.

Functional behavior tests showed also a significant improvement of the motor coordination (RotaRod test) and grip strength (Grips strength test) for 10 I.U./day Epo administration, with no improvement for the low dose.

Taking these results into consideration, two anterograde tract tracers (dextrane amines) were injected in the ipsilateral and contralateral motor cortex of the mice treated with Epo in a higher dose. Histological evaluation of the tracers, both at the level of rubral and facial nucleus showed that functional recovery in these animals was due to an increase of the contralateral projections accompanied from a compensatory decrease of the ipsilateral projections.

Our data support the concept that brain plasticity goes along with coordinated fibers responses both ipsilateral and contralateral to the stroke.