BDNF provides many routes toward STN DBS-mediated disease modification
BDNF provides many routes toward STN DBS-mediated disease modification
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DOI：
10.1002/mds.27535
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发表时间：
2019-01-01
影响因子：
8.6
通讯作者：
Sortwell, Caryl E.
中科院分区：
文献类型：
--
作者：
Fischer, D. Luke;Sortwell, Caryl E.
丘脑底核深部脑刺激 (STN DBS) 可能改善帕金森病 (PD) 疾病的概念存在争议。几项招募晚期帕金森病受试者的临床试验在这个问题上得出了不同的结论。相比之下，一些早期至中期受试者的临床研究表明有缓解疾病的作用。 PD 受试者在诊断后 4 年内基本上不存在壳核的多巴胺能神经支配，这表明任何神经保护治疗，包括 STN DBS，都需要在诊断后立即进行干预。临床前预防和早期干预范例支持 STN DBS 通过增加脑源性神经营养因子 (BDNF) 对黑质纹状体系统的神经保护作用。 STN DBS 诱导的 BDNF 增加提供了多种能够改善帕金森病大脑功能障碍和退化的机制。然而，用于测量脑源性神经营养因子-trkB 信号传导的生物标志物尚无法用于临床研究。如果一项前瞻性临床试验要检验 STN DBS 是否具有疾病缓解作用，我们认为最有力的理由并不依赖于临床前神经保护作用本身，而是取决于 STN DBS 引发的脑源性神经营养因子-trkB 信号传导可以提供疾病缓解的多种潜在机制。 (c) 2018 年作者。 《运动障碍》由 Wiley periodicals, Inc. 代表国际帕金森和运动障碍协会出版。
The concept that subthalamic nucleus deep brain stimulation (STN DBS) may be disease modifying in Parkinson's disease (PD) is controversial. Several clinical trials that enrolled subjects with late-stage PD have come to disparate conclusions on this matter. In contrast, some clinical studies in early- to midstage subjects have suggested a disease-modifying effect. Dopaminergic innervation of the putamen is essentially absent in PD subjects within 4 years after diagnosis, indicating that any neuroprotective therapy, including STN DBS, will require intervention within the immediate postdiagnosis interval. Preclinical prevention and early intervention paradigms support a neuroprotective effect of STN DBS on the nigrostriatal system via increased brain-derived neurotrophic factor (BDNF). STN DBS-induced increases in BDNF provide a multitude of mechanisms capable of ameliorating dysfunction and degeneration in the parkinsonian brain. A biomarker for measuring brain-derived neurotrophic factor-trkB signaling, though, is not available for clinical research. If a prospective clinical trial were to examine whether STN DBS is disease modifying, we contend the strongest rationale is not dependent on a preclinical neuroprotective effect per se, but on the myriad potential mechanisms whereby STN DBS-elicited brain-derived neurotrophic factor-trkB signaling could provide disease modification. (c) 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.