| In the present study, the effects of bilateral subthalamic nuclei (STN) high-frequency stimulation (HFS) in Parkinson's disease (PD) have been investigated using the means of clinical evaluation, microdialysis, molecular biology, behavioral test, immunohistochemistry and the possible mechanisms involved were discussed. The research includes two parts:1. Clinical study of STN-HFS in PD. Forty-one consecutive patients undergone STN-HFS for advanced PD received an evaluation including Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr scale, the Schwab and England Disability Scale , Parkinson's disease Questionnaire Chinese version (PDQ-39), Hospital Anxiety and Depression Scale (HADS) performed by a neurologist a week before surgery and 12 months after the surgical procedure. Significant benefit was obtained in UPDRS, Hoehn and Yahr scale, the Schwab and England Disability Scale, PDQ-39 and HADS. There was correlation between the change obtained in quality of life(PDQ-39SI) and UPDRS secton3 (off medication), Schwab & England (off medication), UPDRS section2 (off medication). In the accordance with our results, bilateral STN-HFS significantly improved the therapeutic outcome and is an effective procedure for treating advanced PD.2. The mechanisms of STN-HFS in PD. We investigated the effect of STN-HFS on striatal dopaminergic metabolism using in vivo microdialysis in freely moving rats. Our data suggest that STN-HFS increases striatal dopaminergic metabolism. Since such changes could be triggered by modification of either protein or gene expression of the rate-limiting enzyme tyrosine hydroxylase (TH), RT-PCR and Western blot of striatal and nigral samples were performed. STN-HFS increased striatal TH protein and gene expression without affecting TH protein expression in substantia nigra. We also applied STN-HFS on 6-hydroxydopamine (6-OHDA) lesioned rats to explore whether the procedure can protect the dopaminergic neurons. |
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