Abstract
Acute stroke causes complex, pathological, and systemic responses that have not been treatable by any single medication. In this study, using a murine transient middle cerebral artery occlusion stroke model, a novel therapeutic strategy is proposed, where blood replacement (BR) robustly reduces infarctions and improves neurological deficits in mice. Our analyses of immune cell subsets suggest that BR therapy substantially decreases neutrophils in blood following a stroke. Electrochemiluminescence detection demonstrates that BR therapy reduces cytokine storm in plasma and ELISA demonstrates reduced levels of matrix metalloproteinase-9 (MMP-9) in the plasma and brains at different time points post-stroke. Further, we have demonstrated that the addition of MMP-9 to the blood diminishes the protective effect of the BR therapy. Our study is the first to show that BR therapy leads to profoundly improved stroke outcomes in mice and that the improved outcomes are mediated via MMP-9. These results offer new insights into the mechanisms of stroke damage.
Highlights
Acute stroke causes complex, pathological, and systemic responses that have not been treatable by any single medication
In this study, using a murine transient middle cerebral artery occlusion stroke model, we present a therapeutic strategy for stroke—a blood replacement (BR) that substitutes stroke mouse blood with whole blood obtained from naive, healthy donor mice
We found that absolute cell numbers of neutrophils (Gr1+), monocytes, CD4+ cells, CD8+ cells, and NK1.1+ cells were significantly increased but CD19+ B cells were decreased at 6 h post stroke compared to controls
Summary
Pathological, and systemic responses that have not been treatable by any single medication. In this study, using a murine transient middle cerebral artery occlusion stroke model, a novel therapeutic strategy is proposed, where blood replacement (BR) robustly reduces infarctions and improves neurological deficits in mice. Current treatments for acute stroke include thrombolytic therapy through the administration of tissue plasminogen activator and the surgical removal of the clot. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) have demonstrated substantially reduced neutrophils and decreased levels of MMP-9 in the blood and brains of stroke mice, which received whole blood obtained from naive donor mice. These results reveal a possible therapy of using blood for brain protection from a stroke
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