Neuroprotective effects of erythropoietin in the rat hippocampus after pilocarpine-induced status epilepticus.
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.
Nadam
Jérémie
J
Laboratory of Integrative Cellular and Molecular Physiology, Centre National de la Recherche Scientifique and Université Claude Bernard Lyon 1 UMR5123, Villeurbanne, France.
Navarro
Fabrice
F
Sanchez
Pascal
P
Moulin
Colette
C
Georges
Béatrice
B
Laglaine
Aël
A
Pequignot
Jean-Marc
JM
Morales
Anne
A
Ryvlin
Philippe
P
Bezin
Laurent
L
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
D000927:Anticonvulsants; D003292:Convulsants; D046911:Macromolecular Substances; D018721:Muscarinic Agonists; D018696:Neuroprotective Agents; D021122:Protein Subunits; D017467:Receptors, Erythropoietin; D010862:Pilocarpine; D004921:Erythropoietin