Abstract
Background: Increasing evidence shows a link between the central nervous system and the immune system in mediating damage, as well as regeneration and repair, following stroke, though most studies focus on T-cell-mediated pathology. While previous work links the B-cell secretion of IL-10 with acute neuroprotection following experimental stroke (PMID: 24374817), the role of B cells in long-term functional recovery is unknown. Hypothesis: The purpose of this study was to assess the protective role of B-cells in improving post-stroke motor function in B-cell deficient mice. Materials and Methods: Adult male transgenic mice expressing human CD20+ (hCD20+) or wild-type (WT) littermate controls (PMID: 17709552) were trained on rotorod for a 2 week duration. Following training, all mice were administered Rituximab (50g ip; PMID: 21359213) daily for 3 days and weekly thereafter. Stroke was induced by a 60-min transient middle cerebral artery occlusion (tMCAo). Post-stroke functional recovery was evaluated 2, 4, 7 and 14 days post-tMCAo. Lymphocytes were isolated from spleen 2 weeks post-tMCAo, stained with antibodies, profiled on a FACS Canto flow cytometer, and analyzed with FlowJo. Results: WT mice recovered to near pre-stroke rotorod performance by 4 days post-tMCAo. In contrast, hCD20+ mice exhibited deficits through 7 days (p<0.05). We confirmed that Rituximab depleted CD20+ B-cells (p<0.05) in the spleen of hCD20+ mice. This post-stroke B-cell depletion reduced CD45+ (p<0.0001) populations, as well as pro-inflammatory CD11b+ macrophage populations (p<0.01). Overall, B-cell depletion increased splenic T-cell percent representation (p<0.001), while decreasing monocyte (p<0.0005) and macrophage (p<0.0001) representation. Conclusions: B-cell depletion in hCD20+ mice prolonged motor deficits in rotorod performance beyond WT mice. B-cell depletion also enhanced a post-stroke immunosuppression of splenic immune cell populations. These data suggest a potential role for B-cells as a therapeutic tool to enhance functional recovery, and counter potentially detrimental post-stroke immunosuppression that contributes to comorbidity during recovery.
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