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Neuroprotective effects of subthalamic nucleus high-frequency stimulation on substantia nigra neurons in a Parkinson's disease rat model

Yu Ma Zhongcheng Wang Jianguo Zhang Huanguang Liu Ying Zhang

中国神经再生研究(英文版)2008,Vol.3Issue(9):1014-1017,4.
中国神经再生研究(英文版)2008,Vol.3Issue(9):1014-1017,4.

Neuroprotective effects of subthalamic nucleus high-frequency stimulation on substantia nigra neurons in a Parkinson's disease rat model

Neuroprotective effects of subthalamic nucleus high-frequency stimulation on substantia nigra neurons in a Parkinson's disease rat model

Yu Ma 1Zhongcheng Wang 2Jianguo Zhang 3Huanguang Liu 2Ying Zhang3

作者信息

  • 1. Department of Functional Neurosurgery,Beijing Neurosurgical Instute,Capital Medical University,Beijing 100050,China
  • 2. Department of Functional Neurosurgery,Beijing Neurosurgical Institute,Capital Medical University,Beijing 100050,China
  • 3. Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China
  • 折叠

摘要

Abstract

BACKGROUND: Deep-brain stimulation has proven to be beneficial in the treatment of Parkinson's disease (PD) patients. OBJECTIVE: To investigate the effects of high-frequency stimulation (HFS) to the subthalamic nucleus (STN) on neuronal apoptosis and apoptosis-related gene expression in the substantia nigra pars compacta, and to analyze the neuroprotective effect of HFS-STN. DESIGN, TIME AND SETTING: Neuronal morphology experiments were performed in the Beijing Nearosurgical Institute from May to December in 2005. MATERIALS: Forty healthy, adult, Sprague Dawley rats were used to establish a PD model with a unilateral microinjection of 6-hydroxydopamine into two target areas of the right medial forebrain bundle. 6-hydroxydopamine was purchased from Sigma (USA); high-frequency electrical stimulator was produced by World Precision Instruments (USA); Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) kit was a product of Nanjing Jiancheng Technology Co., Ltd. (China); and Bcl-2 and Bax protein assay kit were purchased from Wuhan Boster Bioengineering Co., Ltd. (China). METHODS: Forty rats were randomly divided into three groups. The stimulation group (n = 15) received HFS-STN on the day of PD modeling. The PD model group (n = 15) was used to establish the PD model. The control group (n = 1 0) was injected with normal saline containing 0.2 g/L ascorbic acid into two areas of the right medial forebrain bundle. MAIN OUTCOME MEASURES: Survival of dopaminergic neurons in the substantia nigra pars compacta was determined using Nissl staining. Apoptosis of dopaminergic neurons was detected using TUNEL techniques. Expression of anti-apoptotic protein, Bcl-2, and pro-apoptotic protein, Bax, were assayed by immunohistochemistry. RESULTS: Following 6-hydroxydopamine injection, the number of substantia nigra pars compacta neurons was reduced in the stimulation and PD model groups, compared to the control group. At 2 and 4 weeks post-surgery, the grey value of Nissl stained images was significantly less in the PD model and stimulation groups (P < 0.05), and the stimulation group exhibited greater grey values compared to the model group (P < 0.05). At 2 and 4 weeks post-surgery, the number of apoptotic neurons was significantly less in the stimulation group compared to the model group (P < 0.05). In addition, Bcl-2 and Bax expression, as well as the Bcl-2/Bax ratio, was much higher in the stimulation group compared to the model group (P < 0.05). CONCLUSION: HFS-STN has a neuroprotective effect on dopaminergic neurons in the substantia nigra pars eompacta of PD rats by promoting Bcl-2 expression, inhibiting Bax expression, and reducing the number of apoptotic dopaminergic neurons.

关键词

apoptosis/deep-brain stimulation/high-frequency stimulation/Parkinson's disease

Key words

apoptosis/deep-brain stimulation/high-frequency stimulation/Parkinson's disease

分类

医药卫生

引用本文复制引用

Yu Ma,Zhongcheng Wang,Jianguo Zhang,Huanguang Liu,Ying Zhang..Neuroprotective effects of subthalamic nucleus high-frequency stimulation on substantia nigra neurons in a Parkinson's disease rat model[J].中国神经再生研究(英文版),2008,3(9):1014-1017,4.

基金项目

The experiments have been sponsored by the China Postdoctoral Science Fund (No. 20070420399). (No. 20070420399)

中国神经再生研究(英文版)

OACSCDSCI

1673-5374

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