Cord blood rescues stroke-induced changes in splenocyte phenotype and function.
The neuroprotective mechanism of human umbilical cord blood cells (HUCBC) in the rat middle cerebral artery occlusion (MCAO) stroke model remains uncertain. Given the inflammatory sequelae that occur following stroke, we investigated whether HUCBC protection could be derived from the modulation of this immuno-inflammatory event, suggested by the attraction of the HUCBC to the spleen. We found that, following MCAO, rat spleen size was reduced concomitantly with their CD8+ T-cell counts. Interestingly, MCAO-induced spleen size reduction correlated with the extent of ischemic damage, however, HUCBC treatment rescued the spleen weight, splenic CD8+ T-cell counts, as well as the amount of brain injury. Additionally, splenocyte proliferation assays demonstrated that HUCBC treatment opposed MCAO-associated T-cell proliferation by increasing the production of IL-10 while decreasing IFN-gamma. Taken together, these results suggest a novel immunomodulatory mechanism by which HUCBC mediate protection in the rat MCAO model of stroke.
Vendrame
Martina
M
Center for Excellence in Aging and Brain Repair, MDC 78, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Gemma
Carmelina
C
Pennypacker
Keith R
KR
Bickford
Paula C
PC
Davis Sanberg
Cyndy
C
Sanberg
Paul R
PR
Willing
Alison E
AE
D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology* / Q000601:surgery*; D008297:Male; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
D016827:CD8 Antigens; D016207:Cytokines