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经颅超声刺激促进脑源性神经营养因子表达和减少创伤性脑损伤模型中的细胞凋亡。

Transcranial ultrasound stimulation promotes brain-derived neurotrophic factor and reduces apoptosis in a mouse model of traumatic brain injury.

机构信息

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

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

出版信息

Brain Stimul. 2017 Nov-Dec;10(6):1032-1041. doi: 10.1016/j.brs.2017.09.003. Epub 2017 Sep 7.

Abstract

BACKGROUND

The protein expressions of brain-derived neurotrophic factor (BDNF) can be elevated by transcranial ultrasound stimulation in the rat brain.

OBJECTIVE

The purpose of this study was to investigate the effects and underlying mechanisms of BDNF enhancement by low-intensity pulsed ultrasound (LIPUS) on traumatic brain injury (TBI).

METHODS

Mice subjected to controlled cortical impact injury were treated with LIPUS in the injured region daily for a period of 4 days. Western blot analysis and immunohistochemistry were performed to assess the effects of LIPUS.

RESULTS

The results showed that the LIPUS treatment significantly promoted the neurotrophic factors BDNF and vascular endothelial growth factor (VEGF) at day 4 after TBI. Meanwhile, LIPUS also enhanced the phosphorylation of Tropomyosin-related kinase B (TrkB), Akt, and cAMP-response element binding protein (CREB). Furthermore, treatment with LIPUS significantly decreased the level of cleaved caspase-3. The reduction of apoptotic process was inhibited by the anti-BDNF antibody.

CONCLUSIONS

In short, post-injury LIPUS treatment increased BDNF protein levels and inhibited the progression of apoptosis following TBI. The neuroprotective effects of LIPUS may be associated with enhancements of the protein levels of neurotrophic factors, at least partially via the TrkB/Akt-CREB signaling pathway.

摘要

背景

经颅超声刺激可提高大鼠脑源性神经营养因子(BDNF)的蛋白表达。

目的

本研究旨在探讨低强度脉冲超声(LIPUS)对创伤性脑损伤(TBI)的增强 BDNF 的作用及其潜在机制。

方法

采用皮质冲击伤模型,伤后 4 天对损伤区进行 LIPUS 治疗。采用 Western blot 分析和免疫组织化学法评估 LIPUS 的作用。

结果

结果显示,LIPUS 治疗可显著促进 TBI 后第 4 天 BDNF 和血管内皮生长因子(VEGF)等神经营养因子的表达。同时,LIPUS 还增强了原肌球蛋白相关激酶 B(TrkB)、Akt 和环磷酸腺苷反应元件结合蛋白(CREB)的磷酸化。此外,LIPUS 治疗还显著降低了 cleaved caspase-3 的水平。抗 BDNF 抗体抑制了细胞凋亡过程。

结论

总之,损伤后 LIPUS 治疗可增加 BDNF 蛋白水平,并抑制 TBI 后细胞凋亡的进展。LIPUS 的神经保护作用可能与神经营养因子蛋白水平的增强有关,至少部分是通过 TrkB/Akt-CREB 信号通路。

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