The new research may be helpful to the treatment of AD and PD in the future

Stroke, also known as stroke, is one of the major diseases that cause death and morbidity in the world. Stroke is not only the interruption of cerebral blood flow. After ischemic stroke, the blood-brain barrier will be destroyed. The brain tissue releases many substances to the peripheral blood through the open blood-brain barrier to activate the immune system. Activated immune cells will also enter the brain tissue through the open blood-brain barrier to attack brain cells, and then cause complex, pathological and systemic cascade reactions, which can not be cured by any single drug. If the cascade reaction can be terminated in time, it means that the vicious circle may be terminated and the brain tissue will be protected from the secondary damage caused by the further attack of the immune system. The current treatment of acute stroke includes thrombolytic therapy with tissue plasminogen activator and surgical thrombectomy. However, the time window for these treatments is very limited, usually within 3 hours after a stroke. In the clinical treatment of stroke, “time is the brain”, because brain damage is increasing every minute after the stroke. < p > < p > on August 25, nature Communications published a joint study by Ren Xuefang, a research assistant professor in the Department of neuroscience, West Virginia University, and other scientists, introducing a new treatment strategy. The team has been exploring the relationship between immunology and stroke since 2010. After years of research, they found that stroke is not only the pathological changes of brain tissue, but also the hematological changes. The researchers used blood replacement therapy in a mouse model of transient occlusion and reperfusion of the middle cerebral artery, in which the whole blood obtained from the original healthy donor mice replaced the blood of stroke mice. The results showed that BR therapy effectively reduced the infarct size and improved the neurological deficit in mice. In stroke mice, neutrophils in blood and neutrophils were significantly reduced in BR and Br immunotherapy; immunoassay showed a significant reduction in neutrophils in blood after stroke. < / P > < p > this study shows for the first time that BR therapy at 6.5-7 hours after stroke can significantly reduce infarct volume and improve neurological deficits, and the improvement effect is mediated by MMP-9. Blood replacement may be a treatment that can protect the brain from stroke. Replacing 20% of the blood in mice is enough to show a significant reduction in brain damage. The left side of the picture is the control group, and the right side is the experimental group. Brain tissue microscopic image staining analysis showed that blood exchange can protect brain cells from death in stroke mice < / P > < p > the team conducted a series of experiments using the mouse tmcao model, which first proved that blood may play a key role in the evolution of stroke, and then proved that BR therapy can prevent ischemic damage of brain cells, and obtained the following 4 results Important conclusions: < / P > < p > it was found that the larger cerebral infarction occurred at 23 hours after stroke than at 6 hours after stroke, indicating that the damage developed over time in stroke mice with middle cerebral artery occlusion. At the same time, the cell morphology in the blood was changed. These data suggest that blood may play a key role in the evolution of stroke, and that if a blood-based strategy is used within a critical time window, the injured brain may be saved. The researchers used laser speckle imaging to record the changes of cerebral blood flow, Evans blue exudation test to detect the state of blood-brain barrier, cresol violet staining and hematoxylin eosin staining for pathological changes in brain tissue. The results showed that 250 μ L and 500 μ l of whole blood from healthy donors could protect blood-brain barrier, significantly reduce stroke infarction in cerebral cortex, striatum and cerebral hemisphere, and prevent ischemic damage of brain cells. However, 500 μ l of blood has a greater protective effect on brain injury after stroke. To further assess the impact of blood on stroke outcomes, the researchers injected 500 μ l of whole blood from another group of stroke mice with larger cerebral infarction volume into the stroke mice, resulting in a higher mortality rate than the stroke mice cohort that was replaced with blood obtained from healthy donors. These data suggest that it is important to use blood from healthy donors in the treatment of stroke with blood replacement. < / P > < p > it is now recognized that inflammation and the immune system play a key role in acute stroke injury. The team evaluated the blood cell subsets of the recipient stroke mice at three time points before, during and one hour after br. The experimental stroke mice received 500 μ l whole blood from the original donor or stroke mice, while the control group received 500 μ l plasma from the original donor. Compared with the whole blood obtained from stroke mice or plasma from healthy donors, the total number of white blood cells and neurotrophins in the blood of stroke mice obtained from healthy donors were significantly decreased during BR and 1 hour after BR, while the CD4 + cells, CD8 + cells and NK1.1 + cells of monocytes did not change significantly. With the change of the number of blood cells in stroke mice, the levels of pro-inflammatory cytokines and chemokine CXCL1 in plasma also changed. The results showed that BR treatment significantly reduced the levels of proinflammatory cytokines IL-1 β, IL-6, TNF – α and CXCL1 at 8 hours after stroke, and further reduced IL-6, IFN – γ and TNF – α at 23 hours after stroke. The significant changes of CXCL1 in the early stage of stroke suggest that neutrophils may play an important role in the treatment of stroke. White blood cells are the main influencing factors of inflammatory injury after stroke. Br treatment significantly reduced the total absolute cell count of ischemic hemisphere at 8 and 23 hours after stroke. At these two time points, compared with the control group, the accumulation of neurotrophins and macrophages in the affected cerebral hemisphere of stroke mice treated with BR was significantly reduced. These data suggest that BR therapy can reduce inflammation in the central nervous system after stroke. MMP-9 is a protease expressed by neutrophils and macrophages / monocytes. The levels of MMP-9 in the blood of human patients, primates and rodents increased within 2-6 hours after stroke. It is important to further study the role of MMP-9 in the treatment of stroke. Compared with the control group, the level of MMP-9 in plasma of tmcao mice increased at 8 and 23 hours after stroke, but the level of MMP-9 in plasma was significantly decreased by BR treatment. In addition, mmp-9-treated blood replacement aggravated cerebral infarction and neurological deficit in stroke mice, while solvent treated blood significantly improved the prognosis of stroke mice. These results indicate that the presence of MMP-9 reduces the role of Br in the treatment of stroke, suggesting that the decrease of MMP-9 level may be one of the important mechanisms of Br in the treatment of stroke. < / P > < p > first, brain antigens are released through the blood-brain barrier opening and may activate the immune system after a stroke. Therefore, clearing the blood of stroke mice can reduce the level of brain antigen in circulating blood and reduce the activation of brain antigen on immune system. Secondly, clearing the blood of stroke mice can reduce the activated white blood cells and many harmful signals in circulating blood after stroke, such as cytokines, chemokines, proteases and proteases. < / P > < p > Third, it can be observed that blood transfusion may provide nutritional factors for patients with thrombotic thrombocytopenic purpura. It is speculated that oxygen and many other neuroprotective factors may also be provided for stroke brain during blood replacement. In addition, blood exchange can remove the signal of activating the peripheral immune cell cascade reaction, and fresh blood can repair the blood-brain barrier in time and terminate the peripheral cascade reaction. MMP-9 is a key protease signal related to blood-brain barrier leakage, extracellular matrix degradation and cerebral ischemia. Timely reduction of MMP-9 can quickly reduce the cascade reaction after stroke. Further clinical trials are needed to verify the efficacy of whole blood exchange in the treatment of stroke. Professor Ren, the first author of the paper, believes that it is feasible to carry out human studies with whole blood replacement in clinical practice, although there is a certain risk of rejection. At present, the team’s research is further exploring the role of component blood. The blood standard for healthy blood donors has not been established, but in view of the current research results, Professor Ren believes that the level of MMP-9 in blood should not be too high. Cord blood may be helpful in the treatment of stroke. If the whole blood exchange is finally used in clinical practice, it may be helpful for a variety of nervous system diseases, such as Alzheimer’s disease, Parkinson’s disease and so on. As for the other potential effects of blood exchange, the teachers are conservative and think that more experimental data are needed to support the conclusion. Privacy Policy