Biological Mechanism of Fast Near-Infrared Signals in Peripheral Nerves

周围神经快速近红外信号的生物学机制

基本信息

批准号：
7623490
负责人：
PETER R BERGETHON
金额：
$ 34.77万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7623490
关键词：
Accounting Adenosine Adrenergic Agents Affect Age Aging Agonist Algorithms Anatomy Animal Model Applications Grants Basic Science Biological Biological Markers Biological Neural Networks Biopsy Blood Blood Glucose Blood Vessels Blood Volume Blood flow Brain Clinical Coupling Data Analyses Detection Diabetes Mellitus Diagnosis Diagnostic Disease Environment Evaluation Excision Experimental Designs Fiber Filtration Fingerprint Frequencies Gait Goals Health Hemoglobin Homeostasis Human Image Individual Indocyanine Green Injury Intervention Kinetics Knowledge Laboratories Light Link Literature Mammary Neoplasms Measurement Measures Medical Metabolic Methods Modeling Morbidity - disease rate Morphologic artifacts Motion Muscarinics Muscle Nature Near-Infrared Spectroscopy Nerve Nerve Tissue Neural Conduction Neuraxis Neurons Neuropathy Nicotinic Receptors Nitric Oxide Nutrient Optics Organelles Oxygen Pain Pathogenesis Pathway interactions Patient Care Perfusion Peripheral Nerves Peripheral Nervous System Peripheral Nervous System Diseases Physicians Physiological Physiology Play Population Preparation Process Property Rattus Regulation Research Research Methodology Response to stimulus physiology Rodent Rodent Model Role Schwann Cells Series Signal Pathway Signal Transduction Skeletal Muscle Societies Sprague-Dawley Rats Techniques Technology Testing Time Tissues Toxic Environmental Substances Translations Validation Vasa Nervorum adrenergic chemotherapy cholinergic clinical Diagnosis clinical care design disease diagnosis falls hemodynamics human subject in vivo instrument instrumentation light scattering loss of function meetings millisecond mortality nerve supply nervous system disorder new technology noradrenergic novel optical imaging public health relevance receptor relating to nervous system research study sciatic nerve success

项目摘要

DESCRIPTION (provided by applicant): Recently we have been successful in the detection and validation of a novel optical signal associated with peripheral nerve activation in the human. The evidence collected to date supports the hypothesis that the origin of this optical signal is derived from a novel and surprisingly fast-acting neurovascular coupling process associated with the peripheral nerve. The existence of neurovascular coupling in the peripheral nerve is potentially important clinically because it represents a homeostatic process whose disruption may underlie the pathobiology of nerve disease in aging, diabetes and toxic injury. In this proposal we will test the central hypothesis that the near-infrared spectrophotometric (NIRS) signal measured in the peripheral nerve is a result of an intrinsic and normal physiological neurovascular coupling mechanism. First we will adapt our current NIRS instrumentation, probe design, test paradigms and data analysis algorithms to a rat model and using an in vivo sciatic nerve preparation carry out experiments to determine the nature of the anatomical compartment and the stimulus-response relationship coupling to metabolic demand in NIRS. Second we will test the hemodynamic origin of the signal by examining the full spectral fingerprint of the signal and tagging blood with an optical imaging agent. Finally we will establish which component of the NCS-NIRS signal originates from adrenergic, cholinergic or from local signaling pathways by infusing specific agonists and antagonists of 1, 2 , muscarinic, nicotinic receptors and by activating and blocking nitric oxide and adenosine in local pathways. PUBLIC HEALTH RELEVANCE: This research is a translational in bringing new technology and knowledge to the care of patients with nervous system disease especially involving the disease and aging of the peripheral nervous system. This research may help physicians diagnose and treat the nerve damage from diabetes, chemotherapy and environmental toxins that cause significant pain and loss of function and are a burden on individuals and society. This new signal may be a useful target for early clinical diagnosis and potentially intervention of diseases that affect the peripheral nervous system disease.

描述（由申请人提供）：最近，我们在人类中与周围神经激活相关的新型光学信号的检测和验证方面取得了成功。迄今为止收集的证据支持以下假设：该光学信号的起源是从与周围神经相关的新型且令人惊讶的快速作用神经血管耦合过程中得出的。周围神经中神经血管耦合的存在在临床上可能很重要，因为它代表了一种稳态过程，其破坏可能是衰老，糖尿病和毒性损伤中神经疾病的病理生物学的基础。在该提案中，我们将测试中心假设，即在周围神经中测得的近红外分光光度法（NIR）信号是固有和正常生理神经血管偶联机制的结果。首先，我们将对当前的NIR仪器，探针设计，测试范例和数据分析算法调整到大鼠模型中，并使用体内坐骨神经制备进行实验，以确定解剖区室的性质以及刺激反应关系的关系，以偶联到NIRS中的代谢需求。其次，我们将通过检查信号的完整光谱指纹并使用光学成像剂对血液进行检查，以测试信号的血液动力学起源。最后，我们将通过注入1、2的特定激动剂和拮抗剂，毒蕈碱，烟碱受体以及激活和阻断局部途径中的硝酸氧化物和腺苷来确定NCS-NIRS信号的哪个成分源自肾上腺素能，胆碱能或局部信号通路。公共卫生相关性：这项研究是一种转化，将新技术和知识带给神经系统疾病患者的护理，尤其是涉及周围神经系统的疾病和衰老。这项研究可能有助于医生诊断和治疗糖尿病，化学疗法和环境毒素的神经损伤，这些糖尿病会导致严重的疼痛和功能丧失，并给个人和社会带来负担。该新信号可能是早期临床诊断和影响周围神经系统疾病的疾病的潜在干预的有用目标。