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创伤性脑损伤后注射基质细胞衍生因子-1(SDF-1)纳米颗粒可刺激神经干细胞的募集。

Injection of Stromal Cell-Derived Factor-1 (SDF-1) Nanoparticles After Traumatic Brain Injury Stimulates Recruitment of Neural Stem Cells.

作者信息

Zhu Yitong, Wang Yaqiong, Lu Zhaofeng

机构信息

The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan, China.

出版信息

J Biomed Nanotechnol. 2022 Feb 1;18(2):498-503. doi: 10.1166/jbn.2022.3243.

Abstract

Traumatic brain injury (TBI) usually results from direct mechanical damage to the brain, which leads to degeneration and death of the central nervous system (CNS). The migration of neural stem/progenitor cells (NSCs) to brain is essential to various physiological and pathological processes of the CNS. Therefore, NSCs are considered as a promising alternative option for neurological diseases. SDF-1 is one of known chemokines whose receptor CXCR4 is detected in the CNS. We explored the efficacy of nanoparticles loaded with SDF-1 on TBI and analyzed its potential mechanism. After synthesis of SDF-1-loaded microspheres (MS) and -nanoparticles and establishment of animal model of TBI, 50 modeled mice were randomly injected with MS bovine serum albumin (BSA), MS SDF1, or SDF1-loaded nanoparticles and 10 TBI animals were taken as control group. After that, we observed the lesions and examined the characteristics of the nanoparticles and MS. Transwell assay and immunofluorescence were conducted to determine the migration and invasion upon treatments. Nanoparticles and MS encapsulated most of SDF-1, but MS released 100% SDF-1 and the nanoparticles alone released minority (25%) within 2 weeks. As only SDF-1 nanoparticles could induce NSCs to migrate to the injured area, this approach could enhance healing of the lesion with more NSCs around the lesion. Collectively, this study used particles to deliver SDF-1 to the central nervous system with nanoparticles having a longer-lasting release. Injection of nanoparticleloaded SDF-1 would retain the biological activity of SDF-1 and improve neuroblast migration, thereby improving the TBI condition. These findings show great prospect for nanoparticles application in brain injury.

摘要

创伤性脑损伤(TBI)通常是由大脑直接受到机械损伤所致,这会导致中枢神经系统(CNS)发生变性和死亡。神经干细胞/祖细胞(NSCs)向脑部的迁移对于CNS的各种生理和病理过程至关重要。因此,NSCs被认为是治疗神经系统疾病的一种有前景的替代选择。基质细胞衍生因子-1(SDF-1)是一种已知的趋化因子,其受体CXCR4在CNS中被检测到。我们探究了负载SDF-1的纳米颗粒对TBI的疗效,并分析了其潜在机制。在合成负载SDF-1的微球(MS)和纳米颗粒并建立TBI动物模型后,将50只建模小鼠随机注射MS牛血清白蛋白(BSA)、MS SDF1或负载SDF1的纳米颗粒,10只TBI动物作为对照组。之后,我们观察了损伤情况,并检测了纳米颗粒和MS的特性。进行Transwell实验和免疫荧光检测以确定处理后的迁移和侵袭情况。纳米颗粒和MS包裹了大部分SDF-1,但MS在2周内释放了100%的SDF-1,而单独的纳米颗粒仅释放了少数(25%)。由于只有SDF-1纳米颗粒能诱导NSCs迁移至损伤区域,这种方法可通过损伤周围有更多NSCs来促进损伤愈合。总体而言,本研究利用颗粒将SDF-1递送至中枢神经系统,其中纳米颗粒具有更持久的释放效果。注射负载SDF-1的纳米颗粒可保留SDF-1的生物活性并改善神经母细胞迁移,从而改善TBI病情。这些发现显示了纳米颗粒在脑损伤应用中的巨大前景。

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