Erythropoietin treatment improves neurological functional recovery in EAE mice.
Erythropoietin (EPO), originally recognized for its central role in erythropoiesis, has been shown to improve neurological outcome after stroke. Here, we investigated the treatment of experimental autoimmune encephalomyelitis (EAE) in mice with EPO. Mice were treated with recombinant human EPO (rhEPO) upon onset of paresis. Neurological functional tests were scored daily by grading of clinical signs (score 0-5). Hematoxylin and eosin (HE) staining of cerebral tissue was performed to detect inflammatory infiltrates. Double staining for Luxol fast blue and Bielshowsky was used to demonstrate myelin and axons, respectively. Immunohistochemistry was performed to measure the expression of bromodeoxyuridine (BrdU, a marker for cell proliferation), NG2 (a marker for oligodendrocyte progenitor cells) and brain-derived neurotrophic factor (BDNF). Treatment with rhEPO significantly improved neurological functional recovery, reduced inflammatory infiltrates and demyelination, and increased oligodendrocyte progenitor cell proliferation and BDNF+ cells compared to the EAE controls. These data indicate that rhEPO treatment improved functional recovery after EAE in mice, possibly, via stimulating oligodendrogenesis, downregulating proinflammatory infiltrates and by elevating BDNF expression.
Zhang
Jing
J
Department of Neurology, Henry Ford Health Sciences Center, Henry Ford Hospital, Neurology Res (ER 3056), 2799 W Grand Boulevard, Detroit, MI 48202, USA.
Li
Yi
Y
Cui
Yisheng
Y
Chen
Jieli
J
Lu
Mei
M
Elias
Stanton B
SB
Chopp
Michael
M
D000818:Animals; D000941:Antigens / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D019208:Brain-Derived Neurotrophic Factor; D001973:Bromodeoxyuridine; D004921:Erythropoietin; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4