title: Neuroprotective effects of erythropoietin in the rat hippocampus after pilocarpine-induced status epilepticus.
abstract: Neuroprotective functions of erythropoietin (Epo) are thought to involve a heteroreceptor composed of both Epo receptor (Epo-R) and common beta chain (betac). Here, we measured the response of hippocampal Epo system components (Epo, Epo-R and betac) during neurodegenerative processes following pilocarpine-induced status epilepticus (SE), and examined whether recombinant human Epo (rHuEpo) could support neuronal survival. We evidence that Epo is induced in astroglia following SE, in particular within areas displaying delayed neuronal death. In addition, we demonstrate for the first time that rHuEpo reduces considerably hippocampal neurodegeneration following SE. rHuEpo may thus supplement astroglial induction of Epo to promote enhanced hippocampal neuronal survival following SE. We also show that Epo-R is expressed by neurons and astrocytes mainly, while betac is barely detectable in basal conditions and induced in reactive microglia exclusively following SE. Altogether, our results suggest that Epo/rHuEpo exerts neuroprotection, through Epo-R signaling and independently of betac, and, therefore, may be anti-epileptogenic.
authors.affiliation: Laboratory of Integrative Cellular and Molecular Physiology, Centre National de la Recherche Scientifique and Université Claude Bernard Lyon 1 UMR5123, Villeurbanne, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Nadam
authors.forename: Fabrice
authors.initials: F
authors.lastname: Navarro
authors.forename: Pascal
authors.initials: P
authors.lastname: Sanchez
authors.forename: Colette
authors.initials: C
authors.lastname: Moulin
authors.forename: Béatrice
authors.initials: B
authors.lastname: Georges
authors.forename: Aël
authors.initials: A
authors.lastname: Laglaine
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Pequignot
authors.forename: Anne
authors.initials: A
authors.lastname: Morales
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.forename: Laurent
authors.initials: L
authors.lastname: Bezin
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000037:antagonists & inhibitors; D004921:Erythropoietin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D046911:Macromolecular Substances / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine / Q000037:antagonists & inhibitors / Q000633:toxicity; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D046911:Macromolecular Substances; D018721:Muscarinic Agonists; D018696:Neuroprotective Agents; D021122:Protein Subunits; D017467:Receptors, Erythropoietin; D010862:Pilocarpine; D004921:Erythropoietin