Texas Biomedical Device Center, BSB11 800 W Campbell Rd, Richardson, TX, 75080, USA.
Erik Jonsson School of Engineering and Computer Science, Richardson, TX, USA.
Transl Stroke Res. 2021 Feb;12(1):65-71. doi: 10.1007/s12975-020-00829-6. Epub 2020 Jun 25.
Vagus nerve stimulation (VNS) paired with rehabilitative training enhances recovery of function in models of stroke and is currently under investigation for use in chronic stroke patients. Dosing is critical in translation of pharmacological therapies, but electrical stimulation therapies often fail to comprehensively explore dosing parameters in preclinical studies. Varying VNS parameters has non-monotonic effects on plasticity in the central nervous system, which may directly impact efficacy for stroke. We sought to optimize stimulation intensity to maximize recovery of motor function in a model of ischemic stroke. The study design was preregistered prior to beginning data collection (DOI: https://doi.org/10.17605/OSF.IO/BMJEK ). After training on an automated assessment of forelimb function and receiving an ischemic lesion in motor cortex, rats were separated into groups that received rehabilitative training paired with VNS at distinct stimulation intensities (sham, 0.4 mA, 0.8 mA, or 1.6 mA). Moderate-intensity VNS at 0.8 mA enhanced recovery of function compared with all other groups. Neither 0.4 mA nor 1.6 mA VNS was sufficient to improve functional recovery compared with equivalent rehabilitation without VNS. These results demonstrate that moderate-intensity VNS delivered during rehabilitation improves recovery and defines an optimized intensity paradigm for clinical implementation of VNS therapy.
迷走神经刺激 (VNS) 与康复训练相结合可增强中风模型中的功能恢复,目前正在研究用于慢性中风患者。剂量在药理学治疗的转化中至关重要,但电刺激治疗在临床前研究中往往未能全面探索剂量参数。VNS 参数的变化对中枢神经系统的可塑性有非单调的影响,这可能直接影响中风的疗效。我们试图优化刺激强度,以最大限度地恢复缺血性中风模型中的运动功能。该研究设计在开始数据收集之前已预先注册(DOI:https://doi.org/10.17605/OSF.IO/BMJEK)。在接受自动评估前肢功能训练并在运动皮层中发生缺血性损伤后,大鼠被分为接受不同刺激强度(假刺激、0.4 mA、0.8 mA 或 1.6 mA)的康复训练与 VNS 配对的组。与所有其他组相比,中等强度的 0.8 mA VNS 增强了功能恢复。与没有 VNS 的等效康复相比,0.4 mA 或 1.6 mA VNS 均不足以改善功能恢复。这些结果表明,康复期间给予中等强度的 VNS 可改善恢复,并为临床实施 VNS 治疗定义了优化的强度范式。
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