Neuropharma Lab, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília 70910-900, Brazil; Sarah Network of Rehabilitation Hospitals, Brasília 70335-901, Brazil.
Neuropharma Lab, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília 70910-900, Brazil.
J Neurosci Methods. 2022 Oct 1;380:109687. doi: 10.1016/j.jneumeth.2022.109687. Epub 2022 Aug 6.
Deep brain stimulation (DBS) appeared in the therapeutic framework for Parkinson's disease in the late 1980 s and early 1990 s, conceived as an alternative to ablative treatments, using inhibitory electrical stimulation parameters still clinically in force today, with frequencies above 130 Hz, a pulse width of 60 ms and current intensity around 3 mA into deep brain structures, to relieve the motor symptoms of the disease. This context expands into a technique not only restricted to the targets traditionally used in lesional procedures, supported by the knowledge acquired with non-human primate (NHP) animal models during the early 1990 s, initiated by Benazzouz and collaborators. Currently, NHP animal models have lost ground to research models in rodents, which have assumed a prominent position in scientific research on DBS. However, how can an animal so small and different from Homo sapiens provide relevant information that may guide the evolution of treatment for a condition that occurs only in humans, like PD? The scope of this review is to address recent advances in PD pathogeny, DBS principles, and different in vivo experimental DBS models in rodents, their limitations and relevance, as well as the future directions in animal models for scientific research.
脑深部电刺激(DBS)于 20 世纪 80 年代末 90 年代初出现在帕金森病的治疗框架中,被认为是一种替代破坏性治疗的方法,采用的是抑制性电刺激参数,这些参数至今仍在临床应用中,频率高于 130Hz,脉冲宽度为 60ms,电流强度约为 3mA,刺激深度达脑内结构,以缓解疾病的运动症状。这一背景下的技术不仅限于传统的病灶性手术靶点,这一技术得到了 20 世纪 90 年代初由 Benazzouz 及其同事开展的非人类灵长类动物(NHP)模型研究的支持。目前,NHP 动物模型在研究模型中已逐渐失势,啮齿类动物模型在 DBS 的科学研究中占据了重要地位。然而,如此小且与智人如此不同的动物如何提供可能指导治疗人类特有的 PD 等疾病演变的相关信息呢?本综述的目的是探讨 PD 发病机制、DBS 原理以及啮齿动物不同的体内实验性 DBS 模型的最新进展,讨论它们的局限性和相关性,以及未来在动物模型方面的科学研究方向。