COCHLEAR BLOOD FLOW AND NEUROPEPTIDES

这项提案旨在确定耳蜗血流的机制 控制该提案提出了一个假设，即感觉神经元和 P物质（SP）是影响血管张力的重要因素， 耳蜗这项研究有四个具体目标。1)表征 辣椒素敏感的初级感觉神经元的血管舒张作用 经耳蜗前下壁应用辣椒素对耳蜗血流的影响 小脑动脉（AICA）和圆窗膜（RWM）。这将 证明了辣椒素纤维的重要作用， 耳蜗血流调节系统2)测量辣椒素诱导的 耳蜗血管通透性的变化。渗透率 通过静脉内输注胶体银将揭示变化， 随后连续切片耳蜗。该研究将证明 这一神经肽系统在耳蜗液稳态中的作用。3a） 研究SP神经递质对耳蜗血流的影响， 3b）阻断基于SP的辣椒素诱导的耳蜗 血管舒张这将提供直接的证据， SP在耳蜗血流调节中的作用。4a）措施 对辣椒素敏感的豚鼠耳蜗血管舒张功能的变化 神经元和神经肽。动物模型 水肿是耳蜗内稳态病理学的一种重要类型。 这一目标将确定水肿是否也改变了神经肽 血管舒张机制。4b）测量耳蜗血流量（CBF） 糖尿病大鼠应用辣椒素后的变化无创 激光多普勒血流仪测量耳蜗血流的方法 将用于这些实验。

This proposal seeks to define the mechanisms of cochlear blood flow control. The proposal offers the hypothesis that the sensory neurons and Substance P (SP) are important factors contributing to vascular tone in the cochlea. The study has four specific aims. 1) Characterize the vasodilatation effect of capsaicin-sensitive primary sensory neurons on cochlear blood flow by applying capsaicin through the anterior inferior cerebellar artery (AICA) and the round window membrane (RWM). This will demonstrate the significant role of capsaicin fibers as part of the cochlear blood flow regulation system. 2) Measure capsaicin-induced changes in the permeability of cochlear blood vessels. The permeability change will be revealed by intravenous infusion of colloidal silver, followed by serial sectioning of the cochlea. This study will demonstrate a role of this neuropeptide system in cochlear fluid homeostasis. 3a) Characterize the effect of SP neurotransmitter on cochlear blood flow and 3b) pharmacologically block the SP-based, capsaicin-induced cochlear vasodilatation. This will provide direct evidence for a significance of contribution of SP in the regulation of cochlear blood flow. 4a) Measure changes in cochlear vasodilatation produced by the capsaicin-sensitive neurons and neuropeptides in the hydropic guinea pig. The animal model of hydrops is a significant type of homeostatic pathology in the cochlea. This aim will determine if hydrops also alters the neuropeptide vasodilatative mechanisms. 4b) Measure the cochlear blood flow (CBF) change after capsaicin application in diabetic rat. The non-invasive laser Doppler flowmetry method for measurement of cochlear blood flow will be used in these experiments.