Mass transport in the inner-ear fluid

内耳液体中的质量运输

• 批准号: 10580498
• 负责人: Jong-Hoon Nam
• 金额: $ 54万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580498
• 关键词: Acoustic Stimulation; Acoustics; Adult; Agitation; Animals; Apical; Area; Biophysics; Blood; Body Fluids; Characteristics; Cochlea; Cochlear duct; Cochlear nucleus; Computer Models; Custom; Data; Diffusion; Disease; Distant; Drug Delivery Systems; Drug Targeting; Electric Stimulation; Electrodes; Experimental Designs; Fluid Balance; Frequencies; Gene Delivery; Geometry; Gerbils; Goals; Health; Hearing; Hour; Image; Implant; In Vitro; Individual; Inherited; Injections; Kainic Acid; Labyrinth; Learning; Length; Liquid substance; Location; Lymph; Measures; Mechanical Stimulation; Mechanics; Methods; Microfluidics; Modeling; Molecular; Motion; Neurotoxins; Noise; Noise-Induced Hearing Loss; Operative Surgical Procedures; Optical Coherence Tomography; Outer Hair Cells; Pattern; Perforation; Pharmaceutical Preparations; Phase; Physiological; Public Health; Pump; Quality of life; Radial; Resolution; Rest; Salicylic Acids; Sensorineural Hearing Loss; Series; Site; Source; Stimulus; Structure; Temporal bone structure; Testing; Time; Tissues; United States; age related; base; cell motility; design; experimental study; gene therapy; hearing impairment; improved; in silico; in vivo; inner ear diseases; innovation; insight; mechanotransduction; minimally invasive; models and simulation; neural; novel; physiologic model; prevent hearing loss; response; round window; sound; sound frequency; surgical risk; theories; vibration; virtual

PROJECT SUMMARY The inner-ear fluids, unlike other body fluids, are stationary and isolated from the rest of the body. These characteristics give opportunities and challenges in maintaining inner-ear health and in treating inner- ear diseases. Due to the blood-labyrinth barrier, systemic delivery of drugs to the inner ear is highly inefficient. On the other hand, this isolation is an opportunity—drugs can be delivered locally with minimal off-target concerns. Unfortunately, the potential advantage of local delivery has been difficult to capitalize on because of the labyrinthine geometry of the inner ear. Application of drug at any location of the inner ear labyrinth filled with stationary fluids results in high concentration at the application site without reaching distant locations. A current remedy is to create surgical holes in the temporal bone to allow inner-ear fluids to flow despite the risk of surgical damage. We propose minimally invasive and efficient drug delivery mechanism into the inner ear. Specifically, we will develop a method to use sounds as the agitating source for cochlear drug delivery. Recent data regarding OoC micromechanics are both exciting and controversial because new observations do not fit well into existing frameworks for cochlear biophysics. For example, the outer hair cells are widely-acknowledged as the actuator for cochlear amplification. However, the outer hair cells generate force most efficiently at frequencies below the characteristic frequency at most cochlear locations, raising the possibility of additional functions. The proposed project combines two topics that have previously been investigated independently—mechanics and fluid homeostasis of the OoC. By combining these two subjects, we propose the novel hypothesis that active outer hair cells enhance mass transport along the cochlea. We will test the hypothesis with three aims that combine physiological and computational modeling approaches. For Aim 1, experiments in live animals (gerbil) will be used to characterize the effect of sound and outer-hair-cell motility on mass (neurotoxin) transport along the length of the cochlear duct. Aim 2 experiments will use excised cochlear tissues implanted in a novel micro-fluidic chamber to characterize the OoC peristaltic vibrations due to outer-hair-cell motility. For Aim 3, new biophysical computer models will simulate drug delivery along the cochlea, thereby integrating physiological results from Aims 1 and 2. Approximately one out of five adults in the United States has some degree of hearing loss. Multiple common forms of hereditary, age-related, and noise-induced hearing loss are ascribed to malfunctions of cochlear-fluid homeostasis. By investigating cochlear-fluid homeostasis from an innovative point of view (mechanics), this project will provide an explanation on why hearing of high frequency sound is more vulnerable. In the long term, we have ambition to provide a remedy to delay/prevent hearing losses related to fluid-homeostasis.

项目总结 与其他体液不同，内耳液是静止的，与身体的其他部分隔离。 这些特点给维持内耳健康和治疗内耳疾病带来了机遇和挑战。 耳疾。由于血液迷宫的屏障，全身给药到内耳的效率非常低。 另一方面，这种隔离是一个机会--药物可以在当地交付，而偏离目标的可能性最小 担忧。不幸的是，本地交付的潜在优势一直很难利用，因为 内耳的迷宫几何形状。内耳迷路充盈任意部位用药 使用固定流体，可在应用现场实现高浓度，而不会到达较远的位置。一个 目前的治疗方法是在颞骨上开一个外科小孔，让内耳积液可以不计风险地流出。 手术造成的损害。我们提出了微创、高效的内耳给药机制。 具体地说，我们将开发一种使用声音作为耳蜗药输送的搅拌源的方法。 最近关于OOC微观力学的数据既令人兴奋又有争议，因为新的 观察结果并不能很好地适应现有的耳蜗生物物理学框架。例如，外毛细胞 被广泛认为是耳蜗放大的促进器。然而，外毛细胞会产生 在大多数耳蜗处低于特征频率的频率下最有效地施力，提高了 增加功能的可能性。提议的项目结合了两个以前 独立研究--OOC的力学和流体动态平衡。通过将这两个主题结合起来， 我们提出了一个新的假设，即活跃的外毛细胞增强了沿着耳蜗线的物质传输。 我们将结合生理建模和计算建模的三个目标来检验这一假设 接近了。对于目标1，将使用活体动物(沙土鼠)的实验来表征声音和 外毛细胞沿着耳蜗管的长度移动大量(神经毒素)。目标2实验 将使用植入新型微流体室的切除的耳蜗组织来表征OOC蠕动 由于外毛细胞运动而产生的振动。对于目标3，新的生物物理计算机模型将模拟药物 沿着耳蜗线输送，从而整合来自目标1和2的生理结果。 在美国，大约五分之一的成年人有不同程度的听力损失。多重 常见形式的遗传性、年龄相关性和噪音引起的听力损失可归因于 耳蜗液动态平衡。从创新的角度研究耳蜗液的动态平衡 (力学)，这个项目将解释为什么高频声音的听力更多 很脆弱。从长远来看，我们有雄心提供一种补救措施，以延迟/防止与以下有关的听力损失 体液平衡。