Development of swallow evoked potentials as a novel tool to investigate swallowin
吞咽诱发电位的开发作为研究吞咽的新工具
基本信息
- 批准号:8286820
- 负责人:
- 金额:$ 13.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2014-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAge-MonthsAmyotrophic Lateral SclerosisAnimal ModelAnimalsAreaBrain StemCell NucleusCessation of lifeChildhoodControl AnimalDeglutitionDeglutition DisordersDehydrationDevelopmentElectric StimulationElectrodesEvoked PotentialsFutureGoalsHistopathologyHumanImpairmentIndividualKnowledgeLeadLesionLifeLongevityMalnutritionMeasurementMeasuresMethodsMorphologyMotorMusPathogenesisPeripheralPhenotypePopulationProtocols documentationQuality of lifeReflex actionRelative (related person)ResearchResearch ProposalsSensorySignal TransductionSourceStimulusStructure of superior laryngeal nerveSymptomsTechniquesTestingTimeTransgenic AnimalsTransgenic MiceTranslational ResearchUnited StatesVacuoleVagus nerve structureWorkeffective therapyimprovedinnovationinsightmouse modelnervous system disorderneuromechanismneuropathologynovelpublic health relevancerelating to nervous systemresearch studyrespiratoryresponsestem cell therapytool
项目摘要
DESCRIPTION (provided by applicant): The broad, long-term objective of this research proposal is to gain a better understanding of the neuropathology of swallowing impairment (dysphagia) in neurological diseases. Several mouse models currently exist that are suitable and readily available for translational research in neurological diseases. However, relatively little is known about the swallowing function of these mouse models because experimental methods to evaluate the function of the individual neural components of the swallow reflex circuit have not yet been developed. The purpose of the proposed research is to develop an experimental protocol for using brainstem evoked potentials recorded in response to stimulation of the superior laryngeal nerve in mice to quantify the function of the individual sensory, central integration, and motor components of the swallowing reflex circuit. Three specific aims will serve this purpose. Specific Aim 1 will test the hypothesis that it is possible to record swallow evoked potentials (SwEPs) in mice. The optimal stimulus and recording parameters will be identified using 3-4 month old wild-type (C57BL/6J) mice. Waveform morphology (i.e., number of positive and negative peaks, peak-to-peak amplitudes, and peak latencies) will be compared relative the following variables: electrode placement, filter settings, signal amplification, signal averaging, stimulus rate, and stimulus amplitude. Specific Aim 2 will evaluate the utility of the SwEP testing protocol established in Specific Aim 1 to phenotype the swallowing function of a transgenic mouse model of amyotrophic lateral sclerosis (ALS; SOD1-G93A) and nontransgenic littermates at four time points: 1, 2, 3, and 4 months of age. Specific Aim 3 will begin to investigate the generator sources for the SwEP peaks. Histological and immunohistochemical methods will be performed on a subset of animals from Specific Aim 2 to identify the brainstem nuclei (and subnuclei) that are activated during swallowing; these regions also will be investigated for evidence of histopathology (vacuoles). The findings will guide future lesioning experiments and near-field recording studies directed toward positive identification of generator sources of SwEP response peaks. These three specific aims will permit: 1) objective quantification of dysphagia in SOD1-G93A transgenic mice, 2) description of the time-course of neurogenic dysphagia in this strain, and 3) identification of the central neural correlates for dysphagia in this animal model of ALS. The knowledge gained from this work will directly extend the scientific knowledge of normal swallowing and the pathogenesis of dysphagia in ALS. In addition, the SwEP testing protocol established by this work has the potential to be used to identify additional mouse models of dysphagia for various neurological diseases, as well as to quantify the effect of various treatments (e.g., pharmacological agents, stem cell therapy, etc.) on the function of the individual neural components of the swallow relay circuit in these animal models. Thus, development of this experimental protocol in mice may ultimately lead to novel and effective treatment options for dysphagia in humans with neurological diseases.
PUBLIC HEALTH RELEVANCE: Neurogenic dysphagia (i.e., swallowing impairment caused by neurological disorders such as Lou Gehrig's disease) affects approximately 500,000 individuals, including pediatric and adult populations, annually in the United States. Common symptoms include malnutrition, dehydration, and respiratory complications, all of which may result in a poor quality of life and contribute to death in affected individuals. Few effective treatments for neurogenic dysphagia have been identified; therefore, neurogenic dysphagia is certainly an important area for research that has the potential to benefit hundreds of thousands of individuals living within the United States, as well as many more living beyond these borders, who are afflicted by various neurological diseases.
描述(由申请人提供):本研究计划的广泛、长期目标是更好地了解神经系统疾病中吞咽障碍(吞咽困难)的神经病理学。目前存在几种适合且易于用于神经系统疾病转化研究的小鼠模型。然而,人们对这些小鼠模型的吞咽功能知之甚少,因为尚未开发出评估吞咽反射回路各个神经组件功能的实验方法。拟议研究的目的是开发一种实验方案,使用响应小鼠上喉神经刺激记录的脑干诱发电位来量化吞咽反射回路的个体感觉、中枢整合和运动组件的功能。三个具体目标将服务于这一目的。具体目标 1 将测试以下假设:记录小鼠吞咽诱发电位 (SwEP) 是可能的。将使用 3-4 个月大的野生型 (C57BL/6J) 小鼠来确定最佳刺激和记录参数。波形形态(即正峰值和负峰值的数量、峰峰值幅度和峰值延迟)将与以下变量进行比较:电极放置、滤波器设置、信号放大、信号平均、刺激速率和刺激幅度。具体目标 2 将评估具体目标 1 中建立的 SwEP 测试方案的效用,以对肌萎缩侧索硬化症转基因小鼠模型(ALS;SOD1-G93A)和非转基因同窝小鼠在四个时间点(1、2、3 和 4 月龄)的吞咽功能进行表型分析。具体目标 3 将开始研究 SwEP 峰值的发生器源。将对特定目标 2 的一部分动物进行组织学和免疫组织化学方法,以识别吞咽过程中激活的脑干核(和亚核);还将研究这些区域的组织病理学证据(空泡)。这些发现将指导未来的损伤实验和近场记录研究,以积极识别 SwEP 响应峰的发生器源。这三个具体目标将允许:1)客观量化 SOD1-G93A 转基因小鼠的吞咽困难,2)描述该菌株中神经源性吞咽困难的时间过程,以及 3)识别该 ALS 动物模型中吞咽困难的中枢神经相关因素。从这项工作中获得的知识将直接扩展正常吞咽和 ALS 吞咽困难发病机制的科学知识。此外,这项工作建立的 SwEP 测试方案有可能用于识别各种神经系统疾病的其他吞咽困难小鼠模型,以及量化各种治疗(例如药物制剂、干细胞治疗等)对这些动物模型中吞咽中继回路各个神经组件功能的影响。因此,在小鼠中开发这一实验方案可能最终会为患有神经系统疾病的人类吞咽困难带来新颖且有效的治疗选择。
公共卫生相关性:在美国,神经源性吞咽困难(即由神经系统疾病(如卢伽雷氏病)引起的吞咽障碍)每年影响约 500,000 人,包括儿童和成人。常见症状包括营养不良、脱水和呼吸系统并发症,所有这些都可能导致受影响个体的生活质量下降并导致死亡。神经源性吞咽困难的有效治疗方法尚未确定。因此,神经性吞咽困难无疑是一个重要的研究领域,它有可能使生活在美国境内的数十万个人以及生活在美国境外的许多患有各种神经系统疾病的人受益。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
An Experimental Swallow Evoked Potential Protocol to Investigate the Neural Substrates of Swallowing.
研究吞咽神经基质的实验吞咽诱发电位协议。
- DOI:10.1177/2473974x20913542
- 发表时间:2020
- 期刊:
- 影响因子:1.5
- 作者:Kloepper,Ashley;Arnold,Joseph;Ruffolo,Alexis;Kinealy,Brian;Haxton,Chandler;Nichols,Nicole;Takahashi,Kazutaka;Lever,TeresaE
- 通讯作者:Lever,TeresaE
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TERESA E LEVER其他文献
TERESA E LEVER的其他文献
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{{ truncateString('TERESA E LEVER', 18)}}的其他基金
Targeted neuromodulation strategies to delay hypoglossal motoneuron death and preserve tongue strength, function, and structure in a mouse model of ALS
延缓 ALS 小鼠模型舌下运动神经元死亡并保持舌头力量、功能和结构的靶向神经调节策略
- 批准号:
10527999 - 财政年份:2022
- 资助金额:
$ 13.07万 - 项目类别:
Harnessing tongue exercise to enhance neuroplasticity and preserve upper airway function in a novel model of hypoglossal motor neuron degeneration
在舌下运动神经元变性的新型模型中利用舌头运动增强神经可塑性并保留上呼吸道功能
- 批准号:
10433920 - 财政年份:2020
- 资助金额:
$ 13.07万 - 项目类别:
Harnessing tongue exercise to enhance neuroplasticity and preserve upper airway function in a novel model of hypoglossal motor neuron degeneration
在舌下运动神经元变性的新型模型中利用舌头运动增强神经可塑性并保留上呼吸道功能
- 批准号:
10033555 - 财政年份:2020
- 资助金额:
$ 13.07万 - 项目类别:
Harnessing tongue exercise to enhance neuroplasticity and preserve upper airway function in a novel model of hypoglossal motor neuron degeneration
在舌下运动神经元变性的新型模型中利用舌头运动增强神经可塑性并保留上呼吸道功能
- 批准号:
10673603 - 财政年份:2020
- 资助金额:
$ 13.07万 - 项目类别:
Harnessing tongue exercise to enhance neuroplasticity and preserve upper airway function in a novel model of hypoglossal motor neuron degeneration
在舌下运动神经元变性的新型模型中利用舌头运动增强神经可塑性并保留上呼吸道功能
- 批准号:
10380956 - 财政年份:2020
- 资助金额:
$ 13.07万 - 项目类别:
Development of swallow evoked potentials as a novel tool to investigate swallowin
吞咽诱发电位的开发作为研究吞咽的新工具
- 批准号:
7883020 - 财政年份:2010
- 资助金额:
$ 13.07万 - 项目类别:
Development of swallow evoked potentials as a novel tool to investigate swallowin
吞咽诱发电位的开发作为研究吞咽的新工具
- 批准号:
8063194 - 财政年份:2010
- 资助金额:
$ 13.07万 - 项目类别:
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