Implication of the Subthalamic Nucleus in the Pathophysiology and Pathogenesis of Parkinson's Disease

Cell Transplantation

Article

Z. G. Ni¹  A. L. Benabid¹  A. Koudsie¹  A. Benazzouz¹  B. Piallat¹  P. Pollak¹ 

[1] Laboratoire de Neurobiologie Préclinique, INSERM U.318, CHU-Pavillon B, BP 217, 38043 Grenoble Cedex 09, France;

关键词: Parkinson's disease;    Subthalamic nucleus;    Neuroprotection;    High-frequency stimulation;   

DOI  :  10.1177/096368970000900207

来源: Sage Journals

【 摘 要 】

The subthalamic nucleus (STN) has been shown to play an important role in the control of movement and has been considered as a key structure in the functional organization of the basal ganglia. Several studies postulated that the STN plays a critical role in the pathophysiology of Parkinson's disease and that its inhibition or its lesioning can reverse the cardinal motor symptoms. Nevertheless, the beneficial effect was accompanied by dyskinetic abnormal movements. In order to avoid unpleasant and irreversible side effects we used high-frequency stimulation (HFS) of the STN instead of lesions. We have shown that parkinsonian motor symptoms, akinesia, rigidity, and tremor can be alleviated by HFS of the STN in the nonhuman primate model. Side effects were controllable and appeared only at intensities higher than that inducing the improvement of motor symptoms. In severe parkinsonian patients, bilateral STN-HFS greatly improved parkinsonian motor symptoms. Motor fluctuations were attenuated and patients became independent in most activities of daily living. It appears that STN-HFS mimics the effects of lesions by inhibiting its neuronal activity. In a rat model of parkinsonism, we studied the implication of the STN in the excitotoxicity of nigral dopamine cells. We showed that kainic acid lesioning of the STN can protect nigral dopaminergic cells against 6-hydroxydopamine-induced toxicity. The evidence reviewed in the present article clearly demonstrates that the STN is implicated in the pathophysiology and pathogenesis of Parkinson's disease.

【 授权许可】

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