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

• 批准号: 7842553
• 负责人: PETER R BERGETHON
• 金额: $ 34.4万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 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/7842553
• 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

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，我们已经成功地检测和验证了与人类外周神经激活相关的新型光学信号。迄今为止收集的证据支持这一假设，即该光学信号的起源来自与外周神经相关的新颖且令人惊讶的快速作用的神经血管耦合过程。周围神经中神经血管耦合的存在在临床上具有潜在的重要性，因为它代表了一个稳态过程，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基础。在这个建议中，我们将测试中心的假设，近红外分光光度计（NIRS）的信号测量周围神经是一个内在的和正常的生理神经血管耦合机制的结果。首先，我们将调整我们目前的近红外光谱仪器，探针设计，测试范例和数据分析算法，以大鼠模型和使用在体坐骨神经制备进行实验，以确定的解剖室的性质和刺激反应关系耦合到近红外光谱的代谢需求。其次，我们将通过检查信号的全光谱指纹和用光学成像剂标记血液来测试信号的血液动力学来源。最后，我们将通过注入1，2，毒蕈碱，烟碱受体的特异性激动剂和拮抗剂，并通过激活和阻断局部途径中的一氧化氮和腺苷，来确定NCS-NIRS信号的哪一个成分来自肾上腺素能，胆碱能或局部信号传导途径。公共卫生关系：这项研究是一个翻译，把新的技术和知识，以照顾病人的神经系统疾病，特别是涉及疾病和衰老的周围神经系统。这项研究可以帮助医生诊断和治疗糖尿病，化疗和环境毒素造成的神经损伤，这些损伤会导致严重的疼痛和功能丧失，并给个人和社会带来负担。这种新的信号可能是一个有用的目标，早期临床诊断和潜在的干预影响周围神经系统疾病的疾病。