动物实验,斑马鱼,脑血管破裂 z-bo 2020-09-28 440

　　Pathological cerebral hemorrhage includes hemorrhagic stroke and microhemorrhage. Hemorrhagic stroke is one of the main causes of death and disability in the world, mainly hypertension and atherosclerosis. Although it is caused by rupture, microbleeding is caused by the rupture of brain capillaries.

　　In recent years, brain microbleeds have no acute symptoms, but they are all related to age-related cognitive decline and dementia. When a cerebrovascular rupture occurs, it needs to be repaired quickly clinically to avoid aggravation of its symptoms, gradually becoming the most effective treatment plan. Destroying the integrity of vascular endothelium is the main cause of rupture of cerebral blood vessels. Therefore, maintaining cerebrovascular health should help quickly repair endothelial disease and integrity. Endometrial repair can be achieved through the self-renewal of endothelial cells (ECS) and differentiation of endothelial precursor cells derived from bone marrow. However, these two repair mechanisms usually occur during ischemic angiogenesis and are always related to angiogenesis. Macrophages are involved in multiple aspects of brain damage, hemorrhage, blood vessel development and remodeling.

　　After brain injury, the rapid response of microglia mediated by ATP released from damaged parenchymal tissue activates the main immune cells in the brain and engulfed apoptotic cells. After spinal cord or brain injury, recovery requires macrophages. In mouse models of stroke, macrophages prevent the disease from developing into a hemorrhagic infarction. During angiogenesis, it is believed that macrophages can promote the fusion of endothelial tip cells. But until now, there is no direct evidence that macrophages are absolutely necessary for the formation of blood vessels. Through this study, the researchers established a zebrafish brain vascular rupture model, which uses the principle of multiphoton laser to produce damage. The researchers used a multiphoton laser to establish a rupture system of cerebral blood vessels in zebrafish to produce two endothelial ends. After detection by in vivo real-time imaging technology, it was found that macrophages reached the lesion and attached to the two ends of the endothelium. The mechanical traction generated by macrophages pulls the edge of the endothelium, promotes its ligation and promotes rupture repair. In it, no matter how the microfilament depolymerizes or inhibits the activity of phosphoinositide 3-kinase or Rac1, it destroys the connection between macrophages and endothelial cells and destroys the repair of damaged cerebral blood vessels. This study shows that macrophages mediate the repair of cerebral vascular rupture through unexpected direct physical adhesion and mechanical traction.