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经颅超声刺激抑制帕金森病慢性小鼠模型中的神经炎症。

Transcranial Ultrasound Stimulation Suppresses Neuroinflammation in a Chronic Mouse Model of Parkinson's Disease.

出版信息

IEEE Trans Biomed Eng. 2021 Nov;68(11):3375-3387. doi: 10.1109/TBME.2021.3071807. Epub 2021 Oct 19.

Abstract

OBJECTIVE

Neuroinflammation contributes to the development and progression of Parkinson's disease (PD). The aim of this study was to examine whether ultrasound (US) stimulation of the subthalamic nucleus (STN) could suppress the neuroinflammation in a chronic PD mouse model induced by 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).

METHODS

A chronic PD mouse model was built by injections of 20mg/kg MPTP and 250 mg/kg probenecid at 3.5-day intervals for 5 weeks. Mice were randomized into control+sham, MPTP+sham and MPTP+STN+US group. For MPTP+STN+US group, ultrasound wave (3.8 MHz, 50% duty cycle, 1 kHz pulse repetition frequency, 30 min/day) was delivered to the STN the day after MPTP and probenecid injection (the early stage of PD progression). The rotarod test and pole test were performed to evaluate the behavioral changes after ultrasound treatment. Then, the activity of microglia and astrocyte were measured to evaluate the inflammation level in the brain.

RESULTS

Ultrasound stimulation improved the latency to falls in the rotarod test (p = 0.033) and decreased the climbing time in the pole test (p = 0.016) compared with MPTP+sham group. Moreover, ultrasound stimulation reduced the chronic inflammation response as shown in microglia (p = 0.007) and astrocyte (p = 0.032) activation. In addition, HE, Nissl and Tunel staining showed that no brain tissue injury was induced by US.

CONCLUSION

These findings demonstrated that ultrasound stimulation could suppress neuroinflammation in PD mice.

SIGNIFICANCE

Transcranial ultrasound neuromodulation offers a novel approach for Parkinson's disease intervention, potentially through its anti-neuroinflammation functions.

摘要

目的

神经炎症是导致帕金森病(PD)发生和进展的原因之一。本研究旨在探讨超声刺激丘脑底核(STN)是否可以抑制 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的慢性 PD 小鼠模型中的神经炎症。

方法

通过每隔 3.5 天注射 20mg/kg MPTP 和 250mg/kg 丙磺舒,共注射 5 周,构建慢性 PD 小鼠模型。将小鼠随机分为对照组+假手术组、MPTP+假手术组和 MPTP+STN+US 组。对于 MPTP+STN+US 组,在 MPTP 和丙磺舒注射后的第二天(PD 进展的早期阶段),将超声(3.8MHz,50%占空比,1kHz 脉冲重复频率,每天 30 分钟)传递到 STN。在超声治疗后,进行转棒试验和棒试验以评估行为变化。然后,测量小胶质细胞和星形胶质细胞的活性以评估大脑中的炎症水平。

结果

与 MPTP+假手术组相比,超声刺激可提高转棒试验中的跌倒潜伏期(p=0.033),并降低棒试验中的攀爬时间(p=0.016)。此外,超声刺激可减轻小胶质细胞(p=0.007)和星形胶质细胞(p=0.032)激活引起的慢性炎症反应。此外,HE、Nissl 和 Tunel 染色显示超声未引起脑组织损伤。

结论

这些发现表明,超声刺激可抑制 PD 小鼠的神经炎症。

意义

经颅超声神经调节为帕金森病的干预提供了一种新方法,可能通过其抗炎作用。

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