Granulocyte Colony-stimulating Factor and Bone Marrow Mononuclear Cells for Stroke Treatment in the Aged Brain

Author(s): Ana-Maria Buga, Johanna Scheibe, Karoline Moller, Ovidiu Ciobanu, Claudia Posel, Johannes Boltze, Aurel Popa-Wagner.

Journal Name: Current Neurovascular Research

Volume 12 , Issue 2 , 2015

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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.

Keywords: Stem cells, bone marrow, stroke, regenerative therapy, translational medicine.

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Article Details

VOLUME: 12
ISSUE: 2
Year: 2015
Page: [155 - 162]
Pages: 8
DOI: 10.2174/1567202612666150311112550
Price: $58

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