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: 7464661
• 负责人: PETER R BERGETHON
• 金额: $ 36.36万
• 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/7464661
• 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; Caring; Cholinergic Agents; Clinical; Coupling; Data Analyses; Detection; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Disruption; Environment; Evaluation; Excision; Experimental Designs; Fiber; Filtration; Fingerprint; Frequencies; Gait; Goals; Health; Hemoglobin; Homeostasis; Human; Image; Individual; Indocyanine Green; Injury; Intervention; Invasive; 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; Public Health; Rate; 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; design; falls; hemodynamics; human subject; in vivo; infrared spectroscopy; instrument; instrumentation; light scattering; loss of function; millisecond; mortality; nerve supply; nervous system disorder; new technology; noradrenergic; novel; optical imaging; 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一种与人类周围神经激活相关的新型光信号。迄今为止收集到的证据支持这样一种假设，即这种光信号的起源来自与周围神经相关的一种新的、令人惊讶的快速神经血管耦合过程。周围神经中存在的神经血管耦合在临床上具有潜在的重要意义，因为它代表了一种体内平衡过程，其破坏可能是衰老、糖尿病和中毒性损伤中神经疾病的病理生物学基础。在本提案中，我们将检验近红外分光光度（NIRS）信号在周围神经测量是一个内在的和正常的生理神经血管耦合机制的结果的中心假设。首先，我们将把现有的近红外光谱仪器、探针设计、测试范式和数据分析算法应用于大鼠模型，并使用活体坐骨神经制备进行实验，以确定近红外光谱中解剖室的性质以及刺激-反应关系与代谢需求的耦合。其次，我们将通过检查信号的全光谱指纹和用光学显像剂标记血液来测试信号的血流动力学起源。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，以及激活和阻断局部通路中的一氧化氮和腺苷，确定NCS-NIRS信号的哪个成分来自肾上腺素能、胆碱能或局部信号通路。公共卫生相关性：本研究将新技术和知识引入神经系统疾病患者的护理，特别是涉及周围神经系统的疾病和衰老。这项研究可以帮助医生诊断和治疗由糖尿病、化疗和环境毒素引起的神经损伤，这些损伤会导致严重的疼痛和功能丧失，对个人和社会都是一种负担。这一新信号可能是影响周围神经系统疾病的早期临床诊断和潜在干预的有用靶点。