NEUROGENIC CONTROL OF COCHLEAR BLOOD FLOW

本项目将重点研究耳蜗血液的神经源性调节 以及神经源性和内皮介导的相互作用 机制等 控制螺旋血管直径的受体 蜗轴动脉和局部释放的血管活性物质的身份 物质将被确定。局部释放的血管活性物质 将包括来自支配螺旋的神经元的那些 蜗轴动脉和那些从内皮细胞内衬管腔 这艘船 螺旋蜗轴动脉是耳蜗的主要供血动脉。 耳蜗 耳蜗血流调节中的异常已经被发现， 怀疑在各种内耳的病因学中起主要作用 包括突发性和波动性听力损失、梅尼埃氏 疾病、耳鸣和自身免疫相关性听力损失。 的基础 这些病因是耳蜗血管上的受体 以及它们在耳蜗血流调节中的作用。 假设 与受体的存在和释放的 血管活性物质将通过功能测定进行检测， 离体螺旋蜗轴新制剂的研制 动脉 血管直径与血管活性物质的释放 将测量来自神经元元件和来自内皮细胞的细胞毒性。 的 血管直径的测量是最符合生理学的， 相关参数，因为血管直径的变化是 最有效的调节血液流动的方法。 受体将是 利用选择性激动剂测定的药物浓度， 对手。 从神经元释放神经递质， 仍然与孤立的螺旋蜗轴动脉将触发 电场刺激 被释放者的身份 神经递质将通过它们对它们的功能影响来确定。 各自的靶受体，并通过高度特异性的生物发光 比色法 所有的技术都在这个实验室得到了很好的应用。 这 一个项目是从以前的孤立内侧传出神经的项目发展而来的 神经末梢 这两个项目的共同点是关注功能 孤立的神经末梢 而实验性的访问是 以前仅限于连接前的过程，拟议的研究 包括连接前和连接后机制及其复合物 相互作用导致耳蜗血流的调节。 的 预计完成拟议研究后， 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.