Erythropoietin protects hippocampal neurons following status epilepticus

Jérémie Nadam (1) , Fabrice Navarro (1) , Pascal Sanchez (1) , Colette Moulin (1) , Béatrice Georges (1) , Aël Laglaine (1) , Jean-Marc Pequignot (1) , Anne Morales (1) , Philippe Ryvlin (2) , Laurent Bezin (1)

1 PICM - Physiologie intégrative, cellulaire et moléculaire
2 EA1880 - Activation et dysfonctionnements des réseaux neuronaux

Objective: Neuroprotective functions of brain-derived erythropoietin (Epo) are thought to involve both Epo receptor (Epo-R) and common β chain (βc). Here, we measured the response of Epo system (Epo, Epo-R and βc) during neurodegenerative processes occurring following status epilepticus (SE), and examined whether recombinant human Epo (rHuEpo) could support neuronal survival. Methods: We analyzed Epo, Epo-R and βc expression at both messenger RNA and protein levels after pilocarpine-induced SE (Pilo-SE) in the adult rat hippocampus. Potential protective effect of rHuEpo (Eprex®, Janssen-Cilag; 5,000 IU/kg) was investigated 2 weeks after SE. Results: By contrast to Epo and βc, detected in few neurons only in the hippocampus, Epo-R is expressed by a 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. βc is induced in reactive microglia only. Therapeutic administration of rHuEpo reduces considerably neuronal degeneration in the hippocampus. Interpretation: rHuEpo may support astroglial Epo to promote hippocampus neuronal survival following SE, likely through a mechanism involving Epo-R mainly. Paucity of βc in the hippocampus rules out the possibility that βc can play a major role in rHuEpo neuroprotective effects following SE.

Mots clés: astrocytes; erythropoietin receptor; hypoxia-inducible factor-1; aHIF; pilocarpine; status epilepticus

Domaines: Autre [q-bio.OT]

Jérémie Nadam, Fabrice Navarro, Pascal Sanchez, Colette Moulin, Béatrice Georges, et al.. Erythropoietin protects hippocampal neurons following status epilepticus. Neurobiology of Disease, 2007, 25 (2), pp.412-426. ⟨10.1016/j.nbd.2006.10.009⟩. ⟨hal-00018753v4⟩