Construction method and application of transgenic animal with increased blood-brain barrier permeability

Abstract

The invention discloses a construction method and application of a transgenic mouse with increased blood-brain barrier permeability. The method for constructing transgenic engineering mice with increased blood-brain barrier permeability includes modifying the gene to increase the expression of slit protein, and obtaining a transgenic animal model with increased blood-brain barrier permeability. The study found that the overexpression of slit protein caused enlargement of the lateral ventricles of mice, severe damage to the structure of the choroid plexus, and loss of tight junctions of epithelial cells. Observing the vascular structure of the brain of Slit-Tg mice by immunofluorescence staining found that the cerebral vascular bifurcation was less, and the microvessels were more, and the shape of the blood vessels was incomplete and the distribution was irregular. Transmission electron micrographs also showed that the endothelial cells of Slit-Tg mice were damaged, extremely irregular, and the vascular basement membrane was incomplete. Evans? blue? The assay detected the increased permeability of the mice, indicating that the blood-brain barrier permeability of Slit-Tg mice was increased, which can be applied to the animal experiments of central nervous system drugs for the screening, development and efficacy evaluation of neurological drugs.

Description

technical field [0001] The invention relates to a method for constructing a transgenic animal model and its application, in particular to a method for constructing a transgenic animal model with increased permeability of the blood-brain barrier and its application. Background technique [0002] The central nervous system is the most stringent and sensitive system in the human body. Normal neural function requires a highly stringent extracellular environment, where the ion concentrations of sodium, calcium and potassium need to be restricted within a very narrow range. And the metabolic demands of the nervous system are very strong, consuming 20% ​​of the body's oxygen consumption. [0003] The nervous system is very sensitive to many chemical substances. Many substances in the daily diet, although harmless to other organs, are neurotoxic, so there is an interface between the peripheral circulatory system and the central nervous system of mammals , to dynamically adjust ion...

AI Technical Summary

Problems solved by technology

[0013] Studies have shown that in the treatment of intracranial diseases, focused ultrasound can not only ablate the blood-brain barrier, but also partially open the blood-brain barrier, but it still cannot open the blood-brain barrier stably.

[0014] Although there are many ways to open the blood-brain barrier at present, there are problems in varying degrees, such as safety, targeting, tissue compatibility, etc., which seriously restrict the development of central nervous system drugs.

Images