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经颅聚焦超声丘脑治疗与大鼠细胞外 GABA 水平降低有关。

Transcranial focused ultrasound to the thalamus is associated with reduced extracellular GABA levels in rats.

机构信息

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Neuropsychobiology. 2012;65(3):153-60. doi: 10.1159/000336001. Epub 2012 Feb 25.

DOI:10.1159/000336001
PMID:22378299
Abstract

OBJECTIVE

Transcranial focused ultrasound (FUS), with its ability to non-invasively modulate the excitability of region-specific brain areas, is gaining attention as a potential neurotherapeutic modality. The aim of this study was to examine whether or not FUS administered to the brain could alter the extracellular levels of glutamate and γ-aminobutyric acid (GABA), which are representative excitatory and inhibitory amino acid neurotransmitters, respectively.

METHODS

FUS, delivered in the form of a train of pulses, was applied to the thalamus of Sprague-Dawley rats transcranially. Glutamate and GABA were directly sampled from the frontal lobe of the rat brain via a direct microdialysis technique before, during, and after the sonication. The dialysate concentrations were determined by high-performance liquid chromatography.

RESULTS

The individual levels of the neurotransmitters sampled were normalized to the baseline level for each rat. In terms of the changes in extracellular glutamate levels, there was no difference between the FUS-treated group and the unsonicated control group. However, extracellular GABA levels started to decrease upon sonication and remained reduced (approximately 20% below baseline; repeated-measures ANOVA, p < 0.05, adjusted for multiple comparisons) compared to the control group.

CONCLUSION

The ability to modulate region-specific brain activity, along with the present evidence of the ability to modulate neurotransmission, demonstrates the potential utility of FUS as a completely new non-invasive therapeutic modality.

摘要

目的

经颅聚焦超声(FUS)具有非侵入性调节特定脑区兴奋性的能力,作为一种潜在的神经治疗方法正受到关注。本研究旨在探讨 FUS 是否能改变脑内谷氨酸和γ-氨基丁酸(GABA)的细胞外水平,这两种物质分别是代表性的兴奋性和抑制性氨基酸神经递质。

方法

通过颅穿透的方式向 Sprague-Dawley 大鼠的丘脑施加一连串的 FUS 脉冲。在超声治疗前、治疗中和治疗后,通过直接微透析技术直接从大鼠的额叶中取样谷氨酸和 GABA。采用高效液相色谱法测定透析液浓度。

结果

对每个大鼠而言,取样的神经递质的个体水平均与基线水平进行了归一化。就细胞外谷氨酸水平的变化而言,FUS 治疗组与未超声对照组之间没有差异。然而,细胞外 GABA 水平在超声治疗后开始下降,且与对照组相比仍保持降低(约低于基线 20%;重复测量方差分析,p < 0.05,经多重比较调整)。

结论

FUS 具有调节特定脑区活动的能力,以及目前具有调节神经传递的证据,表明 FUS 作为一种全新的非侵入性治疗方法具有潜在的应用价值。

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