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Deep brain stimulation in Parkinson’s disease patients and routine 6‐OHDA rodent models: Synergies and pitfalls
European Journal of Neuroscience ( IF 3.698 ) Pub Date : 2020-08-27 , DOI: 10.1111/ejn.14950
Alessandro Stefani 1 , Rocco Cerroni 1 , Mariangela Pierantozzi 1 , Vincenza D’Angelo 1 , Laura Grandi 2 , Matteo Spanetta 1 , Salvatore Galati 2, 3
Affiliation  

The history of deep brain stimulation for Parkinson's disease (PD) represented a paradigmatic cross‐talk between mammalian disease models and clinical evidence in humans. Fascinating were the results achieved by high frequency stimulation (HFS) into the subthalamic nucleus (STN) of MPTP‐treated primates. An analogous strategy relieved tremor and hypokinetic parameters in PD patients. The 6‐hydroxydopamine (6‐OHDA) rodent model has mastered decades of research, contributing to understanding of the PD pathology. However, this review wonders about the actual synergy between the routine neurotoxic models and PD patients underlying STN‐DBS. At first, some findings collected following 6‐OHDA, promoted dogmatic visions, as the wrong contention that suppression of STN glutamate was the key therapeutic player. Instead, changes of glutamate release are negligible in humans during transition to ON‐state. Besides, the imbalance of basal ganglia endogenous band frequencies, the beta (β) band increase and the cortical‐basal ganglia synchronization, undisputedly shared by models and PD patients, do not govern the whole spectrum of non‐motor PD signs, difficult to investigate in rodents. Furthermore, the tonic release of dopamine, inferred during HFS in rodents, was not replicated in humans. Finally, neurotoxic rodent models describe a ‘pure’ dopamine depletion sparing pathways crucial in parkinsonian phenotypes, that is, noradrenergic and cholinergic ones. Although the utilization of neurotoxic models is still providing major advancements, we pore over these contradictions and try to support possible amendments of neurotoxic models (advocating modern ‘in vivo’ approaches and recordings extending towards motor thalamus) for pursing the development of new DBS technology.

中文翻译:

帕金森氏病患者的深部脑刺激和常规的6-OHDA啮齿动物模型:协同作用和陷阱

帕金森氏病(PD)的深层脑刺激史代表了哺乳动物疾病模型与人类临床证据之间的典范串扰。高频刺激(HFS)进入MPTP处理的灵长类动物的丘脑下核(STN)所获得的结果令人着迷。一种类似的策略可减轻PD患者的震颤和运动功能减退。6-羟基多巴胺(6-OHDA)啮齿动物模型已经掌握了数十年的研究,有助于理解PD病理学。然而,这篇综述想知道常规神经毒性模型与STN-DBS潜在的PD患者之间的实际协同作用。首先,由于6-OHDA引起的一些发现促进了教条主义的视力,因为错误地认为抑制STN谷氨酸是关键的治疗手段。反而,过渡到ON状态期间,人体中谷氨酸盐释放的变化可忽略不计。此外,模型和PD患者毫无争议地共享了基底神经节内源性频带频率失衡,β(β)频带增加和皮质-基底神经节同步性,并不能控制非运动性PD征兆的全部频谱,这很难进行研究。在啮齿动物中。此外,HFS在啮齿动物中推断出的多巴胺的补品释放在人类中没有复制。最后,神经毒性啮齿动物模型描述了在帕金森氏表型中至关重要的“纯”多巴胺消耗备用途径,即去甲肾上腺素能和胆碱能。尽管利用神经毒性模型仍能取得重大进展,
更新日期:2020-08-27
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