Evaluation of the Neuromodulatory Mechanisms of Vagus Nerve Stimulation to Improve Motor Rehabilitation after Stroke

迷走神经刺激改善中风后运动康复的神经调节机制评估

• 批准号: 9973199
• 负责人: SETH ALANSON HAYS
• 金额: $ 33.47万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9973199
• 关键词: Acetylcholine; Activities of Daily Living; Anatomy; Area; Basal Nucleus of Meynert; Basic Science; Brain Injuries; Cell Nucleus; Cerebral hemisphere hemorrhage; Data; Development; Disease; Electric Stimulation; Evaluation; Exhibits; Forelimb; Future; Goals; Human; Impairment; Intervention; Ischemic Stroke; Lesion; Modeling; Motor; Motor Cortex; Movement; Neuromodulator; Neuronal Plasticity; Norepinephrine; Outcome Study; Pathway interactions; Patients; Pharmacology; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Role; Spinal; Stroke; System; Techniques; Testing; Therapeutic Intervention; Training; Translations; Traumatic Brain Injury; Upper Extremity; Viral; behavior test; cholinergic; disability; experimental study; improved; improved functioning; insight; ischemic lesion; locus ceruleus structure; motor function recovery; motor recovery; motor rehabilitation; neuroregulation; noradrenergic; post stroke; pre-clinical; rehabilitation strategy; safety study; stroke model; stroke patient; stroke rehabilitation; stroke therapy; vagus nerve stimulation

PROJECT ABSTRACT Stroke is a leading cause of disability, with an estimated 795,000 cases in the US each year. As many as 70% of patients who suffer a stroke exhibit long-term impairment in upper extremity motor function. The development of rehabilitative strategies to improve the recovery of motor function is of key importance. Neuroplasticity is believed to support recovery after stroke; therefore, manipulations that enhance plasticity may increase recovery. Stimulation of the vagus nerve during motor training drives robust, specific neuroplasticity in rat motor cortex. Recent evidence indicates that vagus nerve stimulation (VNS) delivered during rehabilitative training significantly improves recovery of forelimb function in multiple models of stroke, but the mechanisms underlying VNS-dependent enhancement of recovery are not defined. The cholinergic and noradrenergic neuromodulatory systems are engaged by VNS and represent potential pathways through which VNS may support recovery. We propose to delineate the neuromodulatory pathways and mechanisms by which VNS acts to increase recovery of forelimb motor function after stroke. The first aim of the study will determine whether the cholinergic and noradrenergic systems are required for VNS-dependent enhancement of recovery after stroke. The second aim of the study will evaluate whether direct stimulation of the cholinergic or noradrenergic systems during rehabilitative training is sufficient to enhance recovery. The third aim of the proposal will examine whether anatomical reorganization in descending motor networks is enhanced by VNS therapy to support functional recovery. The results of the proposed experiments will delineate the neuromodulatory pathways and mechanisms by which VNS paired with rehabilitative training enhances recovery after stroke. Insights from these studies will help to determine whether common disease-related and pharmacological factors that influence these neuromodulatory systems may interfere with the beneficial effects of VNS. Ultimately, results from this study will improve the likelihood of successful translation of VNS therapy for stroke patients.

项目摘要 中风是造成残疾的主要原因，美国每年估计有 795,000 例中风。高达70% 中风患者的上肢运动功能出现长期损伤。这 制定康复策略以改善运动功能的恢复至关重要。 神经可塑性被认为有助于中风后的恢复；因此，增强可塑性的操作 可能会增加恢复。运动训练过程中迷走神经的刺激可驱动强健、特异性的神经 大鼠运动皮层的神经可塑性。最近的证据表明迷走神经刺激（VNS） 在康复训练期间，可以显着改善多种中风模型的前肢功能恢复， 但 VNS 依赖性增强恢复的机制尚未明确。胆碱能和 去甲肾上腺素能神经调节系统与 VNS 相关，并代表了潜在的途径 VNS 可能支持恢复。我们建议通过以下方式描述神经调节途径和机制 VNS 的作用是促进中风后前肢运动功能的恢复。该研究的第一个目标是 确定 VNS 依赖性增强是否需要胆碱能和去甲肾上腺素能系统 中风后的恢复。该研究的第二个目的将评估是否直接刺激胆碱能 或去甲肾上腺素能系统在康复训练期间足以促进恢复。第三个目标 该提案将检查 VNS 是否能增强下行运动网络的解剖重组 支持功能恢复的治疗。 所提出的实验结果将通过以下方式描述神经调节途径和机制 VNS 与康复训练相结合可增强中风后的恢复。这些研究的见解将 有助于确定影响这些的常见疾病相关因素和药理因素是否 神经调节系统可能会干扰迷走神经刺激的有益作用。最终，这项研究的结果 将提高 VNS 疗法成功应用于中风患者的可能性。

项目成果

Enhancing plasticity in central networks improves motor and sensory recovery after nerve damage.

增强中枢网络的可塑性可以改善神经损伤后的运动和感觉恢复。

• 发表时间: 2019
• 影响因子: 16.6
• 作者: Meyers, Eric C;Kasliwal, Nimit;Solorzano, Bleyda R;Lai, Elaine;Bendale, Geetanjali;Berry, Abigail;Ganzer, Patrick D;Romero;Rennaker 2nd, Robert L;Kilgard, Michael P;Hays, Seth A
• 通讯作者: Hays, Seth A

Quantitative assessment of cortical somatosensory digit representations after median and ulnar nerve injury in rats.

大鼠正中神经和尺神经损伤后皮质体感手指表征的定量评估。

• 发表时间: 2019-09
• 影响因子: 2
• 作者: Hulsey, Daniel R;Mian, Tabarak M;Darrow, Michael J;Hays, Seth A
• 通讯作者: Hays, Seth A

Parametric characterization of the rat Hering-Breuer reflex evoked with implanted and non-invasive vagus nerve stimulation.

通过植入和非侵入性迷走神经刺激诱发的大鼠 Hering-Breuer 反射的参数表征。

• 发表时间: 2020-05
• 影响因子: 5.3
• 作者: Bucksot, Jesse E;Morales Castelan, Karen;Skipton, Samantha K;Hays, Seth A
• 通讯作者: Hays, Seth A

Validation of a parameterized, open-source model of nerve stimulation.

验证神经刺激的参数化开源模型。

• 发表时间: 2021
• 作者: Bucksot, Jesse E;Chandler, Collin R;Intharuck, Navaporn M;Rennaker, Robert L;Kilgard, Michael P;Hays, Seth A
• 通讯作者: Hays, Seth A

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke.

有针对性的迷走神经刺激用于中风后的康复。

• 发表时间: 2019
• 作者: Engineer, Navzer D;Kimberley, Teresa J;Prudente, Cecília N;Dawson, Jesse;Tarver, W Brent;Hays, Seth A
• 通讯作者: Hays, Seth A