Erythropoietin protects hippocampal neurons during epileptogenesis
Résumé
Objective: Despite the fact that basal brain erythropoietin (Epo) is neuroprotective, Epo system reactivity during neurodegenerative processes remains largely unknown. During the period of intensive neuronal loss occurring in a model of mesial temporal lobe epilepsy (MTLE), we determined Epo system reactivity in the hippocampus and examined whether exogenous recombinant human Epo (rHuEpo) could support neuronal survival. Methods: Epo and Epo-receptor (Epo-R) expression was analyzed after pilocarpine-induced status epilepticus (Pilo-SE) in the hippocampus of adult rats at both messenger RNA and protein levels. Potential protective effects of rHuEpo (Eprex®, Janssen-Cilag; 5,000 IU/kg) administered immediately after, 1 and 3 days after Pilo-SE was investigated 2 weeks later. Results: By contrast to Epo, which is detected in few neurons in the adult rat hippocampus, Epo-R is expressed by a large majority of neurons. Following Pilo-SE, Epo is induced in numerous astrocytes, and hippocampal areas where astroglial induction of Epo is the greatest exhibit a pattern of delayed neuronal death. Therapeutic administration of rHuEpo reduces considerably neuronal degeneration in the hippocampus. Interpretation: Exogenous rHuEpo may support astroglial Epo to promote hippocampus neuronal survival during epileptogenesis and encourages future studies aimed at evaluating beneficial effects of rHuEpo in patients susceptible to develop MTLE.