NEUROGENIC CONTROL OF COCHLEAR BLOOD FLOW

本项目将重点研究耳蜗血的神经源性调节。 血流及其与神经源性和内皮细胞之间的相互作用 机械装置。控制螺旋血管直径的受体 双侧动脉与局部释放血管活性物质的同一性 物质将会被确定。局部释放的血管活性物质 将包括来自支配螺旋的神经元元件的那些 内侧动脉和腔内内皮细胞形成的血管 这艘船。螺旋动脉是上肢的主要供血动脉。 耳蜗骨。耳蜗血流量调节的异常已经被认为 怀疑在各种内耳的病因中起主要作用 包括突发性和波动性听力损失在内的疾病，梅尼埃病 疾病、耳鸣和与自身免疫相关的听力损失。基础到 这些病原体是存在于耳蜗血管上的受体。 以及它们在调节耳蜗血流量中的作用。假设 与受体的存在和释放的身份有关的 血管活性物质将通过基于以下条件的功能分析进行测试 离体旋毛膜体外制剂的新进展 动脉。血管管径与血管活性物质的释放 从神经元元素和从内皮细胞将被测量。这个 测量血管直径是最具生理学意义的- 相关参数，因为血管直径的变化是单一的 最有效的调节血液流动的方法。受体将是 确定的药理利用选择性激动剂和 对抗者。神经递质从神经元释放出来 保留孤立的螺旋蜗牛动脉将被触发 电场刺激。被释放者的身份 神经递质将由它们对其功能的影响来决定。 各自的靶受体和高度特异的生物发光 化验。所有技术都在这个实验室里得到了很好的应用。这 项目从前一个关于孤立的内侧传出的项目进化而来 神经末梢。这两个项目的共同点是对功能的关注 孤立的神经末梢。鉴于试验性的访问是 以前局限于选择前过程，拟议的研究 包括连接前和连接后机制及其复合体 导致耳蜗血流量调节的相互作用。这个 预计拟议研究的完成将为 用于内耳疾病的药物治疗。

This project will focus on the neurogenic regulation of cochlear blood flow and on the interactions between neurogenic and endothelium-mediated mechanisms. Receptors controlling vascular diameter of the spiral modiolar artery and the identity of locally released vasoactive substances will be determined. Locally-released vasoactive substances will include those from neuronal elements innervating the spiral modiolar artery and those from endothelial cells lining the lumen of this vessel. The spiral modiolar artery is the main blood supply of the cochlea. Aberrations in the regulation of cochlear blood flow have been suspected to play a major part in the etiology of a variety of inner ear disorders including sudden and fluctuating hearing loss, Meniere's disease, tinnitus and autoimmune-related hearing loss. Fundamental to these etiologies are the receptors present on the cochlear blood vessels and their function in the regulation of cochlear blood flow. Hypotheses pertaining to the presence of receptors and to the identity of released vasoactive substances will be tested with a functional assay based on newly-developed in vitro preparations of the isolated spiral modiolar artery. The vascular diameter and the release of vasoactive substance from neuronal elements and from the endothelium will be measured. The measurement of the vascular diameter is the most physiologically- relevant parameter since change in the vascular diameter is the single most effective means of regulating blood flow. Receptors will be determined pharmacologically utilizing selective agonists and antagonists. Release of neurotransmitter from neuronal elements which remain with the isolated spiral modiolar artery will be triggered by electric field stimultation. The identity of the released neurotransmitters will be determined by their functional effect on their respective target receptors and by a highly specific bioluminescence assay. All techniques are well established in this laboratory. This project evolved out of the previous one on isolated medial efferent nerve terminals. Common to both projects is the focus on the function of isolated nerve terminals. Whereas the experimental access was previously limited to prejunctional processes, the proposed studies include both pre- and post junctional mechanisms and their complex interactions leading to the regulation of cochlear blood flow. The completion of the proposed studies are expected to provide a foundation for the pharmacologic management of inner ear disorders.