The Experiment Study Of Ultrasound Microbubbles Promote MSCs Transplantation To Across The Blood-brain Barrier

Ischemic stroke is one of the main causes of death and disability. Because the braintissue has the limited self-repair ability, drug treatment can not get ideal effect. Therefore,the people often left permanent neurological function deficiency.Animal experiment and clinical study found that transplantation of embryonic neuralcells and pluripotent stem cells could promote the repair of damaged brain tissue, andimprove neurological deficit symptoms, which suggested that cell transplantation for thetreatment of ischemic cerebral injury is a very promising way. Lots of experiments showthat the bone marrow stromal cells (bone marrow stromal cells, BMSC) transplantationcould migrate, differentiate, and survive in the host brain, which could promote therecovery of neural function after cerebral infarction. The mechanism of transplanted cellspromoted brain damage repair including alternative function of necrotic cells, inhibitingscar and promote local damage nerve regeneration. The local migration of transplanted cellsto the brain damage is a prerequisite for promoting the repair of brain injury. Therefore, themethod to promote local migration of transplanted cells into the brain injury is veryimportant.The blood brain barrier after vein transplantation to brain injury local migration reducethe treatment effect of transplantation. In recent years, the study found that ultrasoundcombined with microbubble technology could temporary open the blood brain barrier safelyand effectively. The technology could promote the drug through the blood brain barrier andimprove brain drug concentration to improve the treatment effect. But ultrasound combinedwith microbubble on the migration of transplanted cells in the brain has not been studied.Therefore, the study of ultrasound combined with microbubble technology transplantationof intravenous bone marrow stromal cells into brain migration is expected to bring a newway for treatment of ischemic stroke. Methods:(1) The evaluation of forebrain ischemia/reperfusion rat model BBBintegrity. Observation of animal model of blood brain barrier integrity in the lightmicroscope and electron microscope, including brain vascular endothelial cell tight junction,basement membrane and glial cell pseudopodia integrity. Observation of the blood brainbarrier structure protein expression, including brain vascular endothelial cells, closedprotein claudin-5basement membrane, collagen IV, laminin astrocyte processes, S100Bprotein. Evaluating blood-brain barrier function of Evans blue extravasation. Observationof light microscope, electron microscope observation of lanthanum nitrate staining.(2)Observing the effects of ultrasound combined with microbubble technology on forebrainischemia/reperfusion blood-brain barrier permeability in rats.(3) Observing the effect ofultrasound combined with microbubble technology on intravenous transplantation of bonemarrow stromal cells into ischemic brain damage zone migration. in vitro amplification andidentification of bone marrow stromal cells; intravenous transplantation of bone marrowstromal cells; bone marrow stromal cells do not compare to cerebral ischemia area to movethe number and distance shift; observation the density of AchE positive fibers.(4)Observing the ultrasound combined with microbubble technology on intravenoustransplantation of bone marrow stromal cells on neural function in rats with water maze testof spatial learning and memory ability.Results:(1) Ischemia reperfusion model can increase the permeability of blood brainbarrier in some degree.(2)The ultrasound microbubble can open cerebral ischemia/reperfusion blood-brain barrier.(3)The ultrasound microbubble can open BBB, andpromote MSCS migration to the brain and increase AchE positive fibers.(4)The ultrasonicmicrobubbles combined with MSCs transplantation can promote the learning and memoryability of forebrain ischemia rats.Conclusion: The blood of ultrasound microbubbles could promote bone marrowmesenchymal cells to intracranial migration, and improve the behavior of forebrainischemia rat ability, MSCs intracranial transplantation could improve cerebral ischemia ratspatial learning ability, but could not improve memory ability. MSCs could be easy get andrapid amplificated, MSCs transplantation for treatment of cerebral ischemia have broadprospects in clinical application. The mechanism of MSCs intracranial transplantation ofultrasound microbubble opening blood brain barrier to promote nerve function improvement still needs be further studied.