Design and Application of Custom Waveforms to Restore and Control Satiety
恢复和控制饱腹感的定制波形的设计和应用
基本信息
- 批准号:10390275
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-10-01 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAbdominal PainAcuteAnimal ExperimentsAnimalsAxonBody WeightBody Weight decreasedBody mass indexChronicClinicalCodeCommunitiesComputer SimulationCountryCross-Over StudiesCustomCutaneousDiabetes MellitusDietDyspepsiaEatingEating BehaviorElectric StimulationElectricityElectrodesElementsEngineeringEnsureEpidemicEructationEsthesiaFatty acid glycerol estersGoalsGrantHealthHigh Fat DietHistologyHumanHypertensionImplantImplanted ElectrodesIndividualInstitutionKnowledgeLeadLearningLibrariesLocationMental DepressionMentorsMethodsModelingNauseaNerveNeuronsObesityOperating RoomsOperative Surgical ProceduresOutcomeOutputOverweightParesthesiaPatientsPatternPeripheralPeripheral NervesPharmaceutical PreparationsPlanning TechniquesPopulationProceduresRattusReportingResearchResearch PersonnelRiskSatiationSensorySeriesSignal TransductionSpinal CordSpinal nerve structureSplanchnic NervesStimulusStomachSurgical complicationTactileTechniquesTestingTexasTherapeuticTimeTouch sensationTrainingUniversitiesVariantVeteransVisceralVomitingWeightWeight GainWorkautonomic nervecareercomorbiditycostdesignexperimental studyfood consumptionhealinghealthy weightimplantationimprovedinsightnerve supplyneural patterningneuromechanismneuroregulationnext generationnovelobese patientsobesity treatmentpreclinical efficacypressurerecruitrelating to nervous systemresponseside effectskillssuccess
项目摘要
Rationale: By 2014, 22 states had an obesity rate ≥30% and none <20%. Costs due to obesity are estimated
at $190B/yr. 72% of Veterans are overweight (45%) or obese (27%), of which 66% have hypertension and
31% have diabetes, the two most common comorbidities associated with obesity. Researchers use vagal
nerve stimulation (VNS) to treat a number of conditions, including obesity. The vagal nerve is the
parasympathetic branch of stomach innervation whereas the lesser-studied splanchnic nerve provides
sympathetic innervation. Splanchnic nerve stimulation (SpNS) has also been used to treat obesity. Sensory
afferents in these nerves relay information about the state of the stomach. How and why VNS and SpNS work
remain unknown. Stimulus parameters vary widely and are often accompanied by side-effects. The limited
success and undesired side effects are hypothesized to be due to the stimulus waveform. This grant seeks to
understand the neural population code associated with stomach distension. It also assesses the effect of novel
VNS and SpNS waveforms designed to mimic the neural population code and reduce side-effects on body
weight in obese rats.
Objective: The objectives of this study are to 1) elucidate the neural mechanisms underlying obesity and 2)
develop and assess the effects of novel stimuli on eating behavior in obese rats. Numerous hypotheses will be
tested through a series of animal experiments over a 4 year time period.
Research Plan and Methodology: During Aim 1, in a series of non-survival experiments, the vagal and
splanchnic nerves will be implanted with electrodes in rats. The rats will be healthy or made overweight or
obese using a moderate or high-fat diet. The animal’s stomach will be distended with an intragastric balloon to
mimic food consumption. Intragastric pressure will be recorded. Nerve recordings will provide insight to the
neural response in the two nerves to stomach filling. The effect of diet and body mass index (BMI) on
discharge pattern will be assessed. During Aim 2, in a series of survival experiments, nerve cuff electrodes will
be implanted around the vagal and splanchnic nerves of rats. The rats will be either a healthy weight or obese.
After healing, the rats will receive VNS, SpNS, or both using either standard time-invariant or novel time-variant
waveforms. A time-variant waveform will be developed from recorded neural patterns and histology obtained in
Aim 1 using 3D finite element models. Effects of stimulus location and waveform type on weight and activity
will be determined over a 20-week period. Histology will be conducted to assess the effects of stimulus on
nerve health.
Immediate and Long-Term Career Goals: The immediate career goal is to become immersed within the field
of obesity research and expand scientific understanding of how electrical stimulation applied to autonomic
nerves can be used to reduce body weight. The long-term career goal is to become an independent clinical
researcher with a lab at the LSCDVAMC that focuses on understanding and controlling the neural mechanism
associated with obesity. Additional goals include 1) continuing to contribute to the local and national VA
research community in the field of neural engineering and 2) advancing the body of scientific knowledge of how
to interface with and control neurons in a manner that leads to natural outcomes. Future research will make
extensive use of computer simulations, animal experiments, and human trials. Patterned nerve stimulation will
be an expertise.
Candidate Training: This CDA2 provides protected time to develop the following new skills: acute and chronic
animal studies; animal surgeries; intraneural and extraneural nerve recording, processing, and analysis;
electrode implantation; autonomic neuromodulation; clinical and surgical treatments of obesity;
理由:到2014年,有22个州的肥胖率≥30%,没有一个州的肥胖率<20%。肥胖造成的成本是估算的
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)
Bilateral Subdiaphragmatic Vagal Nerve Stimulation Using a Novel Waveform Decreases Body Weight, Food Consumption, Adiposity, and Activity in Obesity-Prone Rats.
- DOI:10.1007/s11695-023-06957-w
- 发表时间:2024-01
- 期刊:
- 影响因子:2.9
- 作者:Leinen, Monique;Grandy, Elise F.;Gebel, Lourdes M. Ubeira;Santana, Tahimi Machin;Rodriguez, Amanda L.;Singh, Sundip K.;Fernandez, Michael I.;Dalugdug, Justin C.;Garcia-Colon, Elaine M.;Lybeshari, Kamela;Alexander, Daniel R.;Maura, Maria I.;Gonzalez, Maria D. Cabrera;De Paula Cunha Almeida, Caroline;Anyaso-Samuel, Samuel;Datta, Somnath;Schiefer, Matthew A.
- 通讯作者:Schiefer, Matthew A.
Both high fat and high carbohydrate diets impair vagus nerve signaling of satiety.
高脂肪和高碳水化合物饮食都会损害迷走神经的饱腹感信号传导。
- DOI:10.1038/s41598-021-89465-0
- 发表时间:2021-05-17
- 期刊:
- 影响因子:4.6
- 作者:Loper H;Leinen M;Bassoff L;Sample J;Romero-Ortega M;Gustafson KJ;Taylor DM;Schiefer MA
- 通讯作者:Schiefer MA
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MATTHEW Anthony SCHIEFER其他文献
MATTHEW Anthony SCHIEFER的其他文献
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{{ truncateString('MATTHEW Anthony SCHIEFER', 18)}}的其他基金
Design and testing of a novel circumesophageal cuff for chronic bilateral subdiaphragmatic vagal nerve stimulation (sVNS)
用于慢性双侧膈下迷走神经刺激(sVNS)的新型环食管套囊的设计和测试
- 批准号:
10702126 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Developing a novel stimulus paradigm and interface of vagal nerve stimulation (VNS) to treat obesity
开发一种新的刺激范式和迷走神经刺激(VNS)界面来治疗肥胖
- 批准号:
10597120 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Developing a novel stimulus paradigm and interface of vagal nerve stimulation (VNS) to treat obesity
开发一种新的刺激范式和迷走神经刺激(VNS)界面来治疗肥胖
- 批准号:
10425537 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Toward Closed-Loop Control of Homeostatic Blood Pressure Following Spinal Cord Injury
脊髓损伤后稳态血压的闭环控制
- 批准号:
10311117 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Design and Application of Custom Waveforms to Restore and Control Satiety
恢复和控制饱腹感的定制波形的设计和应用
- 批准号:
9795377 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Design and Application of Custom Waveforms to Restore and Control Satiety
恢复和控制饱腹感的定制波形的设计和应用
- 批准号:
10011592 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Neural Interface and Control Design to Restore Sensation in Amputees
用于恢复截肢者感觉的神经接口和控制设计
- 批准号:
8278363 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Neural Interface and Control Design to Restore Sensation in Amputees
用于恢复截肢者感觉的神经接口和控制设计
- 批准号:
8499094 - 财政年份:2012
- 资助金额:
-- - 项目类别:
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