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利用低强度脉冲超声刺激增强星形胶质细胞中的神经营养因子以发挥对脑部疾病的神经保护作用。

Enhancement of Neurotrophic Factors in Astrocyte for Neuroprotective Effects in Brain Disorders Using Low-intensity Pulsed Ultrasound Stimulation.

作者信息

Yang Feng-Yi, Lu Wen-Wei, Lin Wei-Ting, Chang Chi-Wei, Huang Sin-Luo

机构信息

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.

出版信息

Brain Stimul. 2015 May-Jun;8(3):465-73. doi: 10.1016/j.brs.2014.11.017. Epub 2014 Dec 4.

DOI:10.1016/j.brs.2014.11.017
PMID:25558041
Abstract

BACKGROUND

Astrocytes play an important role in the growth and survival of developing neurons by secreting neurotrophic factors.

OBJECTIVE

The goal of this study was to investigate how low-intensity pulsed ultrasound (LIPUS) stimulation directly affects brain astrocyte function.

METHODS

Here, we report that LIPUS stimulation increased protein levels of BDNF, GDNF, VEGF, and GLUT1 in rat brain astrocytes as measured by western blot analysis. Histological outcomes including demyelination and apoptosis were examined in rats after administration of aluminum chloride (AlCl3).

RESULTS

At the mechanistic level, integrin inhibitor (RGD peptide) attenuated the LIPUS-induced neurotrophic factor expression. The data suggest that neurotrophic factor protein levels may be promoted by LIPUS through activation of integrin receptor signaling. In addition, LIPUS stimulation protected cells against aluminum toxicity as demonstrated by an increase in the median lethal dose for AlCl3 from 3.77 to 6.25 mM. In in vivo histological evaluations, LIPUS significantly reduced cerebral damages in terms of myelin loss and apoptosis induced by AlCl3.

CONCLUSIONS

The results of this study demonstrate that transcranial LIPUS is capable of enhancing the protein levels of neurotrophic factors, which could have neuroprotective effects against neurodegenerative diseases.

摘要

背景

星形胶质细胞通过分泌神经营养因子在发育中神经元的生长和存活中发挥重要作用。

目的

本研究的目的是探讨低强度脉冲超声(LIPUS)刺激如何直接影响脑星形胶质细胞功能。

方法

在此,我们报告通过蛋白质印迹分析测量,LIPUS刺激增加了大鼠脑星形胶质细胞中BDNF、GDNF、VEGF和GLUT1的蛋白质水平。在给予氯化铝(AlCl3)后,对大鼠的脱髓鞘和凋亡等组织学结果进行了检查。

结果

在机制水平上,整合素抑制剂(RGD肽)减弱了LIPUS诱导的神经营养因子表达。数据表明,LIPUS可能通过激活整合素受体信号传导来促进神经营养因子蛋白水平。此外,LIPUS刺激保护细胞免受铝毒性,AlCl3的半数致死剂量从3.77 mM增加到6.25 mM就证明了这一点。在体内组织学评估中,LIPUS在AlCl3诱导的髓鞘损失和凋亡方面显著减少了脑损伤。

结论

本研究结果表明,经颅LIPUS能够提高神经营养因子的蛋白质水平,这可能对神经退行性疾病具有神经保护作用。

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