title: Erythropoietin amplifies stroke-induced oligodendrogenesis in the rat.
abstract: BACKGROUND
  Erythropoietin (EPO), a hematopoietic cytokine, enhances neurogenesis and angiogenesis during stroke recovery. In the present study, we examined the effect of EPO on oligodendrogenesis in a rat model of embolic focal cerebral ischemia.
  
  
  RESULTS
  Recombinant human EPO (rhEPO) at a dose of 5,000 U/kg (n = 18) or saline (n = 18) was intraperitoneally administered daily for 7 days starting 24 h after stroke onset. Treatment with rhEPO augmented actively proliferating oligodendrocyte progenitor cells (OPCs) measured by NG2 immunoreactive cells within the peri-infarct white matter and the subventricular zone (SVZ), but did not protect against loss of myelinating oligodendrocytes measured by cyclic nucleotide phosphodiesterase (CNPase) positive cells 7 days after stroke. However, 28 and 42 days after stroke, treatment with rhEPO significantly increased myelinating oligodendrocytes and myelinated axons within the peri-infarct white matter. Using lentivirus to label subventricular zone (SVZ) neural progenitor cells, we found that in addition to the OPCs generated in the peri-infarct white matter, SVZ neural progenitor cells contributed to rhEPO-increased OPCs in the peri-infarct area. Using bromodeoxyuridine (BrdU) for birth-dating cells, we demonstrated that myelinating oligodendrocytes observed 28 days after stroke were derived from OPCs. Furthermore, rhEPO significantly improved neurological outcome 6 weeks after stroke. In vitro, rhEPO increased differentiation of adult SVZ neural progenitor cells into oligodendrocytes and enhanced immature oligodendrocyte cell proliferation.
  
  
  CONCLUSIONS
  Our in vivo and in vitro data indicate that EPO amplifies stroke-induced oligodendrogenesis that could facilitate axonal re-myelination and lead to functional recovery after stroke.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yier
authors.initials: Y
authors.lastname: Toh
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Santra
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001369:Axons; D002455:Cell Division; D004921:Erythropoietin / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins; D020521:Stroke / Q000473:pathology*
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin