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Granulocyte colony-stimulating factor and bone marrow mononuclear cells for stroke treatment in the aged brain
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Buga, Ana-Maria, Scheibe, Johanna, Moller, Karoline, Ciobanu, Ovidiu, Posel, Claudia, Boltze, Johannes and Popa-Wagner, Aurel (2015) Granulocyte colony-stimulating factor and bone marrow mononuclear cells for stroke treatment in the aged brain. Current Neurovascular Research, 12 (2). pp. 155-162. doi:10.2174/1567202612666150311112550
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Official URL: http://dx.doi.org/10.2174/156720261266615031111255...
Abstract
Ischemic stroke swiftly induces a wide spectrum of pathophysiological sequelae, particularly in the aged brain. The translational failure of experimental therapies, might partially be related to monotherapeutic approaches, not address potential counter-mechanisms sufficiently or within the best time window. For example, therapeutic effects relying on stem/progenitor cell mobilization by granulocyte-colony stimulating factor (G-CSF), require approximately a week to become manifest, which is potentially beyond the optimal timing. Here, We tested the hypothesis that treating post-stroke aged rats with the combination of bone marrow-derived mononuclear cells (BM MNC) and G-CSF improves the long term (56 days) functional outcome by compensating the delay before G-CSF effects come to full effect. 1x106 syngeneic BM MNC per kg bodyweight (BW) with G-CSF (50µg/kg, given intraperitoneal by via the jugular vein to aged Sprague- Dawley rats, six hours post-stroke. This process was repeated daily, for a 28 day period. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunohistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period. Daily G-CSF treatment led to a robust and consistent improvement of neurological function, but did not alter final infarct volumes. The combination of G-CSF and BM MNC, did not further improve post-stroke recovery. The lack of an additional benefit may be due to interaction between both approaches, and to a lesser extent, in the insensitivity of the aged brains’ regenerative mechanisms. Also considering recent findings on other tandem approaches involving G-CSF in animal models featuring relevant co-morbidities, we conclude that such combination therapies are not the optimal approach to treat the acutely injured aged brain.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Current Neurovascular Research | ||||
| Publisher: | Bentham Science Publishers | ||||
| ISSN: | 1567-2026 | ||||
| Official Date: | 2015 | ||||
| Dates: |
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| Volume: | 12 | ||||
| Number: | 2 | ||||
| Page Range: | pp. 155-162 | ||||
| DOI: | 10.2174/1567202612666150311112550 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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