title: Granulocyte colony-stimulating factor (G-CSF) treatment in combination with transplantation of bone marrow cells is not superior to G-CSF treatment alone after cortical stroke in spontaneously hypertensive rats.
abstract: Granulocyte-colony stimulating factor (G-CSF) and bone marrow derived mononuclear cells (BM-MNCs) have both been shown to improve functional outcome following experimental stroke. These effects are associated with increased angiogenesis and neurogenesis. In the present study, we aimed to determine synergistic effects of G-CSF and BM-NMC treatment on long-term structural and functional recovery after photothrombotic stroke. To model the etiology of stroke more closely, we used spontaneously hypertensive (SH) rats in our experiment. Bone marrow derived mononuclear cells transplantation was initiated 1 h after the onset of photothrombotic stroke. Repeated G-CSF treatment commenced immediately after BM-MNC treatment followed by daily injections for five consecutive days. The primary endpoint was functional outcome after ischemia. Secondary endpoints included analysis of neurogenesis and angiogenesis as well as determination of infarct size. Granulocyte-colony stimulating factor treated rats, either in combination with BM-MNC or alone showed improved somatosensory but not gross motor function following ischemia. No beneficial effect of BM-MNC monotherapy was found. Infarct volumes were comparable in all groups. In contrast to previous studies, which used healthy animals, post-stroke neurogenesis and angiogenesis were not enhanced by G-CSF. In conclusion, the combination of G-CSF and BM-MNC was not more effective than G-CSF alone. The reduced efficacy of G-CSF treatment and the absence of any beneficial effect of BM-MNC transplantation might be attributed to hypertension-related morbidity.
authors.affiliation: Department of Neurology, University of Münster Münster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Diederich
authors.affiliation: Department of Neurology, University of Münster Münster, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Neurology, University of Münster Münster, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Beuker
authors.affiliation: Department of Neurology, University of Münster Münster, Germany.
authors.forename: Jan-Kolja
authors.initials: JK
authors.lastname: Strecker
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology Leipzig, Germany ; Translational Center for Regenerative Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Daniel-Christoph
authors.initials: DC
authors.lastname: Wagner
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology Leipzig, Germany ; Translational Center for Regenerative Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.affiliation: Department of Neurology, EVK Bielefeld Bielefeld, Germany.
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
authors.affiliation: Department of Neurology, University of Münster Münster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
keywords: G-CSF; angiogenesis; bone marrow cells; functional recovery; neurogenesis; neuroregeneration; spontaneously hypertensive rat (SHR); stroke