COCHLEAR BLOOD FLOW AND NEUROPEPTIDES

这项建议试图定义耳蜗血流量的机制 控制力。该提议提出了一种假设，即感觉神经元和 P物质(SP)是引起血管张力的重要因素。 耳蜗管。这项研究有四个具体目标。1)描述 辣椒素敏感初级感觉神经元的血管扩张作用 辣椒素通过前下耳道的耳蜗血流量 小脑动脉(AICA)和圆窗膜(RWM)。这将是 证明辣椒素纤维作为 耳蜗血流量调节系统。2)测量辣椒素诱导的 耳蜗血管通透性的变化。通透性 变化将通过静脉输注胶体银来揭示， 然后是耳蜗骨的连续切片。这项研究将证明 这一神经肽系统在耳蜗液稳态中的作用。3A) SP神经递质对耳蜗血流量影响的实验研究 3b)药理阻断SP诱导的辣椒素诱导的耳蜗肌 血管扩张。这将提供直接证据，证明 SP在耳蜗血流量调节中的作用4A)措施 辣椒素敏感引起的耳蜗血管舒张性改变 水肿性豚鼠的神经细胞和神经肽。动物模型 积水是耳蜗内一种重要的动态平衡病理。 这个目的将确定积水是否也改变了神经肽。 血管扩张机制。4b)测量耳蜗血流量(CBF) 糖尿病大鼠应用辣椒素后的变化。非侵入性的 激光多普勒血流仪测量耳蜗血流量的方法 将在这些实验中使用。

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.