Biological Mechanism of Fast Near-Infrared Signals in Peripheral Nerves

描述(由申请人提供)：最近，我们成功地检测和验证了一种与人类周围神经激活相关的新的光学信号。到目前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于与周围神经相关的一种新颖且快得令人惊讶的神经血管耦合过程。周围神经血管偶联的存在在临床上具有潜在的重要意义，因为它代表着一种动态平衡的过程，这种平衡的破坏可能是衰老、糖尿病和中毒损伤中神经疾病的病理生物学基础。在这项提案中，我们将检验中心假设，即在周围神经中测量到的近红外光谱(NIRS)信号是内在的和正常的生理神经血管耦合机制的结果。首先，我们将把我们目前的近红外光谱仪器、探针设计、测试范式和数据分析算法应用于大鼠模型，并使用体内坐骨神经制备进行实验，以确定近红外光谱中解剖间隔的性质以及与代谢需求耦合的刺激-反应关系。其次，我们将通过检查信号的全光谱指纹并使用光学显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，M受体和烟碱受体的特定激动剂和拮抗剂，以及通过激活和阻断局部通路中的一氧化氮和腺苷，来确定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：这项研究为神经系统疾病患者的护理带来了新的技术和知识，特别是涉及周围神经系统疾病和衰老的患者。这项研究可能有助于医生诊断和治疗糖尿病、化疗和环境毒素造成的神经损伤，这些疾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。这种新的信号可能是早期临床诊断和潜在干预影响周围神经系统疾病的疾病的有用靶点。

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.