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.
Highlights
Stroke is a lethal disease, yet it disables more than it kills
We hypothesized that the combination of Granulocyte-colony stimulating factor (G-CSF) and bone marrow derived mononuclear cells (BM-MNCs) is more effective than either treatment alone because transplantation of exogenous BM-MNCs can bridge the gap until G-CSF mobilizes endogenous BM-MNCs into the blood
All experiments were performed on a total number of 55 animals
Summary
Stroke is a lethal disease, yet it disables more than it kills. Better controls of risk factors in preventing stroke and improved treatment options for those who have had a stroke are essential for diminishing its devastating consequences. The stimulation of endogenous bone marrow cells by the granulocyte colony-stimulating growth factor (G-CSF) and the transplantation of bone marrow mononuclear cells (BM-MNCs) were shown to enhance regeneration in a large number of animal stroke studies (Schneider et al, 2005; Giraldi-Guimarães et al, 2009; Diederich et al, 2012b). Mechanisms underlying G-CSF and BM-MNC induced functional recovery after stroke include the potentiation of endogenous neurogenesis and angiogenesis as well as an increased dendritic plasticity (Lee et al, 2005; Schneider et al, 2005). Granulocyte-colony stimulating factor mediates its actions on these mechanisms by the mobilization of bone marrow cells and by direct neuronal effects (Schneider et al, 2005). According to its genuine function, G-CSF might increase the survival of transplanted BM-MNCs and thereby improve their efficacy
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