Department of Neurology, Parkinson Expertise Center, University Medical Center Groningen, University of Groningen, Hanzeplein 1 AB-51, 9700RB, Groningen, The Netherlands.
Animal Science Department, Biomedical Primate Research Centre (BPRC), P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands.
Sci Rep. 2021 Jun 3;11(1):11751. doi: 10.1038/s41598-021-91391-0.
Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been clinically investigated in Alzheimer's disease (AD) and Lewy body dementia (LBD). However, the clinical effects are highly variable, which questions the suggested basic principles underlying these clinical trials. Therefore, preclinical and clinical data on the design of NBM stimulation experiments and its effects on behavioral and neurophysiological aspects are systematically reviewed here. Animal studies have shown that electrical stimulation of the NBM enhanced cognition, increased the release of acetylcholine, enhanced cerebral blood flow, released several neuroprotective factors, and facilitates plasticity of cortical and subcortical receptive fields. However, the translation of these outcomes to current clinical practice is hampered by the fact that mainly animals with an intact NBM were used, whereas most animals were stimulated unilaterally, with different stimulation paradigms for only restricted timeframes. Future animal research has to refine the NBM stimulation methods, using partially lesioned NBM nuclei, to better resemble the clinical situation in AD, and LBD. More preclinical data on the effect of stimulation of lesioned NBM should be present, before DBS of the NBM in human is explored further.
核基底节区(NBM)的深部脑刺激(DBS)已在阿尔茨海默病(AD)和路易体痴呆(LBD)的临床研究中进行了研究。然而,临床效果差异很大,这对这些临床试验的基本原理提出了质疑。因此,本文系统地回顾了关于 NBM 刺激实验设计及其对行为和神经生理方面的影响的临床前和临床数据。动物研究表明,NBM 的电刺激可增强认知、增加乙酰胆碱的释放、增加脑血流、释放几种神经保护因子,并促进皮质和皮质下感受野的可塑性。然而,这些结果向当前临床实践的转化受到了阻碍,因为主要使用的是具有完整 NBM 的动物,而大多数动物都是单侧刺激的,并且仅在有限的时间内使用不同的刺激模式。未来的动物研究必须改进 NBM 刺激方法,使用部分损伤的 NBM 核,以更好地模拟 AD 和 LBD 的临床情况。在进一步探索 NBM 的 DBS 之前,应该提供更多关于刺激损伤的 NBM 效果的临床前数据。