电刺激迷走神经对实验性帕金森病大鼠具有有益作用：涉及迷走神经传入通路的证据。

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway.

机构信息

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, Japan.

出版信息

Brain Stimul. 2023 Mar-Apr;16(2):594-603. doi: 10.1016/j.brs.2023.03.003. Epub 2023 Mar 12.

DOI:10.1016/j.brs.2023.03.003

PMID:36914065

Abstract

BACKGROUND

Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined.

OBJECTIVE

To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats.

METHODS

Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively.

RESULTS

Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects.

CONCLUSION

Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

摘要

背景

迷走神经刺激（VNS）在中枢神经系统疾病的临床前模型中发挥神经保护和抗炎作用，包括帕金森病（PD）。用于实验模型的 VNS 设置仅限于单次或间歇性短时间刺激。我们开发了一种可对大鼠进行连续刺激的 VNS 设备。迄今为止，使用连续电刺激对 PD 进行迷走神经传入或传出选择性刺激的效果仍有待确定。

目的

研究连续和选择性刺激迷走神经传入或传出纤维对帕金森病大鼠的影响。

方法

大鼠分为 5 组：完整 VNS、传入 VNS（左侧 VNS 存在左侧尾侧迷走神经切断术）、传出 VNS（左侧 VNS 存在左侧额侧迷走神经切断术）、假手术、迷走神经切断术。大鼠同时接受左侧迷走神经袖带电极植入和左侧纹状体 6-羟多巴胺给药。电刺激在 6-OHDA 给药后立即开始，并持续 14 天。在传入 VNS 和传出 VNS 组中，分别在袖带电极的远端或近端解剖迷走神经，以模拟传入或传出迷走神经纤维的选择性刺激。