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Mapping Stomach Autonomic Circuitry and Function for Neuromodulation of Gastric Disorders

绘制胃自主神经回路和功能以调节胃部疾病的神经调节

基本信息

批准号：
9286967
负责人：
TERRY L. POWLEY
金额：
$ 200.44万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-24 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9286967
关键词：
Action Potentials Acute Address Adverse effects Algorithms Animal Model Animals Architecture Axon Biological Assay Biological Neural Networks Brain Stem Chemicals Chronic Clinic Clinical Communities Complex Devices Digestion Disease Eating Eating Disorders Educational workshop Electrodes Electrolytes Elements Epidemic Equipment and supply inventories Family suidae Feedback Fiber Foundations Functional Magnetic Resonance Imaging Future Gastric Emptying Gastroesophageal reflux disease Gastroparesis Generations Growth Hormones Human Image Indium Ingestion Institution Investigation Knowledge Label Laboratories Lead Learning Liquid substance Location Magnetic Resonance Imaging Maps Measures Medical Research Medicine Modeling Molecular Monitor Nausea and Vomiting Nerve Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Operative Surgical Procedures Organ Outcome Patients Pattern Peripheral Nerves Pharmaceutical Preparations Pharmacological Treatment Pharmacotherapy Phenotype Physiological Physiology Protocols documentation Qualifying Rattus Reflex action Reflux Refractory Regulation Reporting Research Research Personnel Resolution Resource Sharing Response to stimulus physiology Role Secondary to Series Signal Transduction Site Smooth Muscle Specimen Stimulus Stomach Stomach Diseases Taxonomy Techniques Technology Testing Therapeutic Time Tissues Translations United States National Institutes of Health Validity and Reliability Wireless Technology clinical application combat connectome data archive design diabetic gastroparesis disorder control feeding implantable device innovation nerve supply neural circuit neuroregulation next generation pre-clinical relating to nervous system research study response sound standard measure

项目摘要

Project Summary Two series of complementary experiments, conducted by our exceptionally qualified team of 11 investigators from eight state-of-the-art laboratories at four institutions, will close critical gaps in the current characterization of the autonomic connectome controlling stomach function. These proposed synergistic anatomical and functional investigations will form the needed foundation for neuromodulation protocols that can correct shortcomings in past, first-generation bioelectronic attempts to ameliorate and monitor gastric disorders. Building on recent advances in mapping of vagal circuits, many reported by our research team, SA 1 will finish inventories of the efferent and afferent terminal phenotypes, analyze their collateral specializations, establish their regional distributions, and identify chemical taxonomies of their target tissues. We will also compare the neural circuitry of the human (and pig, an ideal large animal preclinical proof-of-principle model) stomach with that of the rat model to facilitate future translational extrapolations. The analyses of SA 1 will use a suite of high-definition neural tracing, immunohistochemical and molecular protocols, along with advanced imaging and morphometric techniques, that our team has adapted to autonomic circuits. SA 1 will focus on those elements in gastric neural network that may be most relevant to informing SA 2 and identify additional localized sites in the stomach wall where focal stimulation will have strong therapeutic potential. In functional assessments, SA 2 will identify optimal locations for both highly selective vagal stimulation (VNS) and precise surgical placement between the exit of the vagus from the brainstem and the target sites of the axons within the stomach wall and will determine the best stimulation protocols for augmenting gastric physiology. SA 2 will use state-of-the-art closed-loop stimulator technologies, algorithms, and electrodes (previously designed and robustly proven by investigators on our research team) and assess the reliability, validity, and stability of the VNS by employing a battery (≥ 6) of acute, short-term, and long-term non-invasive endpoints. The team will use data archiving and resource sharing platforms that are universally accessible to all research and medical communities.

项目总结