Cerebral Blood Flow Responses to Extracranial Alternating Current Brain Stimulation in CVN Mouse Model of Alzheimer's Disease: A Pilot Study Determining Optimal Dose.

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Neuromodulation Pub Date : 2025-07-18 DOI:10.1016/j.neurom.2025.06.002

Simone Degan, Yu Feng, Carol Colton, Stephen Schmidt, Angel V Peterchev, Dennis A Turner

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引用次数: 0

Abstract

Introduction: Insufficient metabolic supply in response to neural demand is a key mechanism of degeneration in Alzheimer's disease [AD]. However, extracranial alternating current [AC] stimulation can increase cerebral blood flow [CBF] and metabolic substrate supply to the brain. In this work, we investigate in an initial, pilot study the optimal dosage of extracranial AC brain stimulation appropriate for long-term treatment to retard degeneration in a mouse AD model [CVN].

Materials and methods: We applied extracranial AC (0.5-2.0 mA; 10 Hz; 20-second bursts) to CVN and control C57Bl/6 mice while measuring CBF and intracerebral electric field in vivo in anesthetized animals, and behavioral responses in awake animals.

Results: We found a significant, diffuse increase in cortical CBF (2.6% increase at 0.75 mA) and intracerebral electric field (6.36mV/mm gradient at 0.75 mA) in response to extracranial AC brain stimulation in both CVN and control mice. In awake, behaving mice, the optimal dose of stimulation was 0.75 mA (in 30-second bursts), causing no adverse behavioral effects.

Conclusion: Scheduled (at fixed times) or demand-triggered (during dynamic metabolic need) bursts of extracranial brain stimulation could enhance CBF to improve brain metabolic supply. The goal of this potential AD treatment is to alleviate mismatches between neural metabolic demand and brain substrate supply, to prevent AD phenotypic disease progression. Based on these pilot data, 0.75 mA is an optimal stimulation treatment dose leading to an appreciable net change in CBF, at a moderate intracranial electrical field, while also indicating behavioral tolerability, now being implemented in a long-term treatment trial.

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阿尔茨海默病CVN小鼠模型脑血流对颅外交流电刺激的反应：确定最佳剂量的初步研究

导论：神经需求引起的代谢供应不足是阿尔茨海默病[AD]退行性变的关键机制。然而，颅外交流电（AC）刺激可增加脑血流量（CBF）和脑代谢性底物供应。在这项工作中，我们在一项初步的、初步的研究中探讨了颅外交流脑刺激的最佳剂量，适合于长期治疗，以延缓小鼠AD模型的变性[CVN]。材料与方法：应用颅外交流电(0.5 ~ 2.0 mA；10赫兹;C57Bl/6小鼠作为对照，在麻醉动物体内测量CBF和脑内电场，以及清醒动物的行为反应。结果：我们发现CVN和对照小鼠在颅外交流脑刺激下，皮质CBF （0.75 mA时增加2.6%）和脑内电场（0.75 mA时梯度为6.36mV/mm）显著弥漫性增加。在清醒、行为正常的小鼠中，最佳刺激剂量为0.75 mA（30秒爆发），没有造成不良行为影响。结论：预定（定时）或需求触发（动态代谢需要时）的颅外脑刺激可增强脑血流，改善脑代谢供应。这种潜在的阿尔茨海默病治疗的目标是减轻神经代谢需求和脑底物供应之间的不匹配，以防止阿尔茨海默病的表型疾病进展。根据这些试验数据，0.75 mA是一个最佳的刺激治疗剂量，可以在中等颅内电场下导致CBF的明显净变化，同时也表明行为耐受性，目前正在一项长期治疗试验中实施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuromodulation 医学-临床神经学

CiteScore

6.40

自引率

3.60%

发文量

978

审稿时长

54 days

期刊介绍： Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational, and basic science research in the field. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer-reviewed articles on the technology, science, and clinical application of devices that interface with the nervous system to treat disease and improve function.