Neuroprotective effect of a new rhEPO analogue with low erythropoietic activity

CASALIS, PABLO; THOMALE, ULRICH W.; CEAGLIO, NATALIA; MATTIO, MÓNICA; PEROTTI, NORMA; ETCHEVERRIGARAY, MARINA; KRATJE, RICARDO; OGGERO, MARCOS

Huerta Grande. Córdoba.

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Sociedad Argentina de Investigación en Neurociencia

Although recombinant human erythropoietin (rhEPO) is a promising therapeutic agent for neuroprotection, its use might lead to hematological side-effects such as red cell mass increase and platelet aggregation.  Using a rat model of traumatic brain injury (TBI), the present study explored the neuroprotective potential of a novel physicochemically-related rhEPO analogue with low erythropoietic activity (rhNEPO). Male Sprague-Dawley rats were subjected to a moderate focal cortical contusion. Following TBI, animals were treated with daily ip. applications of rhNEPO or rhEPO. After 3 days, rats were killed in order to measure contusion volume, hippocampal neuronal loss and neural apoptosis. Hemoglobin was also quantified before TBI and after therapy. Treatments with rhNEPO or rhEPO were able to slightly reduce the damaged area without significant differences in the contusion volumes. Interestingly, both molecules significantly reduced the loss of CA2-3 hippocampal neurons in about 50% when compared with placebo and they prevented apoptosis in the pericontusional area. Besides, only rhEPO increased hemoglobin, suggesting that rhNEPO might be a good candidate for TBI therapy because it shows the same neuroprotective action than rhEPO but does not elicit erythropoiesis significantly.