NEUROGENIC CONTROL OF COCHLEAR BLOOD FLOW

耳蜗血流的神经控制

• 批准号: 6564037
• 负责人: A. Philine Wangemann
• 金额: $ 26.25万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564037
• 关键词: acetylcholine; adenosine triphosphate; artery; brain circulation; calcitonin gene related peptide; cochlea; dopamine; electrostimulus; endothelin; gerbil /jird; nerve endings; neuropharmacology; nitric oxide; norepinephrine; substance P; vasoactive intestinal peptide; vasodilation; video microscopy

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.

该项目将重点关注耳蜗血液的神经源性调节 流以及神经源性和内皮介导之间的相互作用 机制。 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 物质将被测定。局部释放的血管活性物质 将包括那些来自支配螺旋的神经元元素 蜗轴动脉和内壁内皮细胞的动脉 这艘船。 蜗轴螺旋动脉是心脏的主要血液供应 耳蜗。 耳蜗血流调节失常 怀疑在多种内耳的病因学中起主要作用 疾病，包括突发性和波动性听力损失、梅尼埃氏症 疾病、耳鸣和自身免疫相关的听力损失。 基本的 这些病因是耳蜗血管上存在的受体 及其在调节耳蜗血流中的功能。 假设 关于受体的存在和释放的身份 血管活性物质将通过基于以下的功能测定进行测试 新开发的分离螺旋蜗轴体外制剂 动脉。 血管直径和血管活性物质的释放 将测量来自神经元元件和内皮的细胞。 这 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单一的 调节血流最有效的方法。 受体将是 利用选择性激动剂在药理学上确定 对手。 从神经元元件中释放神经递质 保留在孤立的螺旋蜗轴动脉中将被触发 电场刺激。 被释放者身份 神经递质将由其对神经递质的功能影响决定 各自的目标受体并通过高度特异性的生物发光 化验。 所有技术均已在该实验室得到完善。 这 项目是从前一个关于孤立内侧传出的项目演变而来的 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。 而实验访问是 以前仅限于预结过程，拟议的研究 包括连接前和连接后机制及其复杂的 相互作用导致耳蜗血流的调节。 这 拟议研究的完成预计将为 用于内耳疾病的药物治疗。