title: Bone marrow cell transplantation time-dependently abolishes efficacy of granulocyte colony-stimulating factor after stroke in hypertensive rats.
abstract: OBJECTIVE
  We aimed to determine a possible synergistic effect of granulocyte colony-stimulating factor (G-CSF) and bone marrow-derived mononuclear cells (BM MNC) after stroke in spontaneously hypertensive rats.
  
  
  METHODS
  Male spontaneously hypertensive rats were subjected to middle cerebral artery occlusion and randomly assigned to daily injection of 50 μg/kg G-CSF for 5 days starting 1 hour after stroke (groups 1, 2, and 3) with additional intravenous transplantation of 1.5×10E7 BM MNC per kilogram at 6 hours (group 2) or 48 hours (group 3) after stroke, or control treatment (group 4). Circulating leukocyte counts and functional deficits, infarct volume, and brain edema were repeatedly assessed in the first week and first month.
  
  
  RESULTS
  G-CSF treatment led to a significant neutrophilia, to a reversal of postischemic depression of circulating leukocytes, and to a significantly improved functional recovery without affecting the infarct volume or brain edema. BM MNC cotransplantation was neutral after 6 hours, but reversed the functional effect of G-CSF after 48 hours. Short-term investigation of combined G-CSF and BM MNC treatment at 48 hours indicated splenic accumulation of granulocytes and transplanted cells, accompanied by a significant rise of granulocytes in the circulation and the ischemic brain.
  
  
  CONCLUSIONS
  G-CSF improved functional recovery in spontaneously hypertensive rats, but this effect was abolished by cotransplantation of BM MNC after 48 hours. In the spleen, transplanted cells may hinder the clearance of granulocytes that were massively increased by G-CSF. Increased circulation and infiltration of granulocytes into the ischemic brain may be detrimental for stroke outcome.
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.). claudia.poesel@izi.fraunhofer.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pösel
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Johanna
authors.initials: J
authors.lastname: Scheibe
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Alexander
authors.initials: A
authors.lastname: Kranz
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Viktoria
authors.initials: V
authors.lastname: Bothe
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Elfi
authors.initials: E
authors.lastname: Quente
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Wenke
authors.initials: W
authors.lastname: Fröhlich
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Franziska
authors.initials: F
authors.lastname: Lange
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.affiliation: From the Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (C.P., J.S., A.K., E.Q., W.F., F.L., J.B., D.-C.W.); Translational Centre for Regenerative Medicine, Leipzig, Germany (A.K., V.B., E.Q., W.F., J.B., D.-C.W.); EVK Bielefeld, Bethel, Neurologische Klinik, Bielefeld, Germany (W.-R.S.); Department of Neurology, University of Münster, Germany (J.M.); and Massachusetts General Hospital and Harvard Medical School, Boston (J.B.).
authors.forename: Daniel-Christoph
authors.initials: DC
authors.lastname: Wagner
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D001921:Brain / Q000503:physiopathology; D003131:Combined Modality Therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D008297:Male; D009504:Neutrophils; D051381:Rats; D011918:Rats, Inbred SHR; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D013997:Time Factors
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: cell- and tissue-based therapy; granulocyte colony-stimulating factor; immune system; stroke