Biological Mechanism of Fast Near-Infrared Signals in Peripheral Nerves

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，我们将使当前的NIRS仪器、探针设计、测试范例和数据分析算法适应大鼠模型，并使用体内坐骨神经制备物进行实验，以确定解剖区室的性质以及与代谢相耦合的刺激-反应关系NIRS中的需求。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。公共卫生相关性：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。

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.