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Bone marrow cell transplantation time-dependently abolishes efficacy of granulocyte colony-stimulating factor after stroke in hypertensive rats
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Pösel, Claudia, Scheibe, Johanna, Kranz, Alexander, Bothe, Viktoria, Quente, Elfi, Fröhlich, Wenke, Lange, Franziska, Schäbitz, Wolf-Rüdiger, Minnerup, Jens, Boltze, Johannes and Wagner, Daniel-Christoph (2014) Bone marrow cell transplantation time-dependently abolishes efficacy of granulocyte colony-stimulating factor after stroke in hypertensive rats. Stroke, 45 (8). pp. 2431-2437. doi:10.1161/STROKEAHA.113.004460 ISSN 0039-2499.
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Official URL: http://dx.doi.org/10.1161/STROKEAHA.113.004460
Abstract
Background and Purpose—
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Stroke | ||||
| Publisher: | Lippincott Williams & Wilkins | ||||
| ISSN: | 0039-2499 | ||||
| Official Date: | 1 August 2014 | ||||
| Dates: |
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| Volume: | 45 | ||||
| Number: | 8 | ||||
| Page Range: | pp. 2431-2437 | ||||
| DOI: | 10.1161/STROKEAHA.113.004460 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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