title: Granulocyte colony-stimulating factor and bone marrow mononuclear cells for stroke treatment in the aged brain.
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. 1x10(6) syngeneic BM MNC per kg bodyweight (BW) with G-CSF (50 µg/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.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Buga
authors.forename: Johanna
authors.initials: J
authors.lastname: Scheibe
authors.forename: Karoline
authors.initials: K
authors.lastname: Moller
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Ciobanu
authors.forename: Claudia
authors.initials: C
authors.lastname: Posel
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.affiliation: Department of Psychiatry, University of Medicine Rostock, Gehlsheimerstr. 20, 18147 Rostock, Germany. aurel.popa-wagner@med.uni-rostock.de.
authors.forename: Aurel
authors.initials: A
authors.lastname: Popa-Wagner
mesh_terms: D000375:Aging; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000473:pathology; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000473:pathology / Q000628:therapy*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor