对深部脑刺激治疗神经、发育和神经精神疾病的啮齿动物研究的系统综述。
Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders.
机构信息
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
出版信息
Transl Psychiatry. 2024 Apr 11;14(1):186. doi: 10.1038/s41398-023-02727-5.
Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.
深部脑刺激(DBS)调节功能障碍网络中的局部和广泛连接。在几个患者群体中观察到了积极的结果;然而,治疗的确切机制仍不清楚。转化 DBS 研究旨在回答这些问题,并为推进该领域提供知识。在这里,我们系统地回顾了涉及神经、发育和神经精神障碍模型的 DBS 研究文献,为围绕该主题的当前科学景观提供了综合概述。按照 PRISMA 指南对文献进行了系统分析。共纳入 407 篇原始文章。数据提取重点关注研究特征,包括刺激方案、行为结果和作用机制。随着时间的推移,发表的文章数量有所增加,包括 16 个大鼠模型和 13 个小鼠模型,这些模型中的转基因或健康动物暴露于外部因素以诱导症状。大多数研究针对端脑结构,刺激设置不同。纳入的研究中有 85.8%报告了积极的行为结果。在精神和神经发育障碍模型中,DBS 诱导的效应与中脑边缘多巴胺能回路中单胺和神经元活动的变化有关。对于运动障碍,DBS 通过调节纹状体多巴胺能系统来改善症状。在痴呆和癫痫模型中,海马的细胞和分子方面的变化被证明是改善症状的基础。尽管将发现从临床前转化到临床环境存在局限性,但啮齿动物研究为我们当前对疾病的病理生理学和 DBS 机制的认识做出了重要贡献。直接抑制/兴奋神经活动,即 DBS 调节大脑网络中病理性振荡活动,是其机制的主要理论之一。然而,仍然存在机制、最佳靶点和参数方面的基本问题,需要更好地理解这些问题,以改善这种治疗方法,并根据患者的主要症状提供更个体化的治疗。