To determine the role of blood in stroke, we conducted a dose–response experiment of BR on stroke outcomes using a murine tMCAO model (Fig. The data suggest that blood might play a critical role in the evolution of a stroke and the injured brain may be rescued if a blood-based strategy is used during a critical time window. 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. We have also demonstrated that stroke alters cellular profiles in blood following a 90 min tMCAO and ischemic reperfusion in mice (Supplementary Fig. We determined larger infarction from stroke mice at 23 h compared to 6 h, indicating that the injury evolves over time after removals of filaments in MCA-occluded stroke mice. Using an experimental stroke animal model of tMCAO, we demonstrated that infarction evolves following a 90 min tMCAO and reperfusion (Supplementary Fig. The BR therapy improves stroke outcomes in post-stroke mice
![thebrain 9 excel file preview thebrain 9 excel file preview](https://ec.europa.eu/eurostat/statistics-explained/images/b/bd/Gross_value_added_in_rural_regions%2C_2010_(%_share_of_total_value_added).png)
These results reveal a possible therapy of using blood for brain protection from a stroke. Further, addition of MMP-9 in blood diminishes therapeutic effects of the BR therapy. In addition, 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. Following the treatment, we demonstrate that the BR therapy significantly reduces the cytokine storm in the plasma. We have demonstrated that the BR performed at 6.5~7 h following a stroke robustly reduces infarct volume and improves neurological deficits. In this study, using a murine transient middle cerebral artery occlusion (tMCAO) 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. MMP-9 also interacts with chemokines 8 and cytokines 9, 10, 11, causing a further cascade of post-ischemic cerebral inflammation that leads to degeneration in brain tissue and exacerbates stroke outcomes. Activated neutrophils secret proteinases such as matrix metalloproteinase-9 (MMP-9), which may cause BBB leakage, extracellular matrix degradation, and evolution of cerebral ischemia 7. A hyperinflammatory condition, including an increase in inflammatory cells, cytokines, and chemokines in circulating blood has been documented in stroke 6. Following BBB disruption after ischemic stroke, a pathological and systemic reaction may be initiated. Dynamic breaches of the blood–brain barrier (BBB) has been observed in experimental stroke animal models 3, 4 and stroke patients 5. In the clinical field of stroke, the mantra is “time is brain,” because infarct evolves every minute following a stroke.Ī stroke is more than just a disruption of blood flow to the brain stroke pathophysiology is a progressive and systemic response to brain injury 2.
![thebrain 9 excel file preview thebrain 9 excel file preview](https://i.stack.imgur.com/7HYSJ.jpg)
![thebrain 9 excel file preview thebrain 9 excel file preview](https://ars.els-cdn.com/content/image/1-s2.0-S221112472030824X-fx1.jpg)
However, these methods have limited time windows.
#Thebrain 9 excel file preview Activator#
Current treatments for acute stroke include thrombolytic therapy through the administration of tissue plasminogen activator and the surgical removal of the clot. These results offer new insights into the mechanisms of stroke damage.Ī stroke remains a major cause of morbidity and mortality globally 1. 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. Further, we have demonstrated that the addition of MMP-9 to the blood diminishes the protective effect of the BR therapy. 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. Our analyses of immune cell subsets suggest that BR therapy substantially decreases neutrophils in blood following a stroke. 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. Acute stroke causes complex, pathological, and systemic responses that have not been treatable by any single medication.