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.

项目摘要 与其他体液不同，内耳流体是固定的，并且与身体的其余部分分离。 这些特征为维持内耳健康和治疗内部健康方面带来了机会和挑战 耳病。由于血液临床屏障，将药物全身传递到内耳效率高。 另一方面，这种隔离是一个机会 - 可以以最少的脱离目标在本地交付毒品 关注。不幸的是，由于本地交付的潜在优势很难利用 内耳的迷宫几何形状。在内耳迷宫的任何位置使用药物 固定液体在应用地点导致高浓度，而无需到达遥远的位置。一个 当前的补救措施是在临时骨骼中创建手术孔，以使内耳液流动目的地风险 手术损伤。我们提出了最小的侵入性和有效的药物输送机制到内耳。 具体而言，我们将开发一种使用声音作为人工耳蜗递送的搅拌来源的方法。 有关OOC微力学的最新数据既令人兴奋又有争议，因为新 观察结果不太适合用于人工耳蜗生物物理学的现有框架。例如，外毛细胞 被广泛地被视为人工耳蜗的执行器。但是，外毛细胞会产生 在大多数人耳蜗的特征频率以下的频率下，强力最有效 其他功能的可能性。拟议的项目结合了两个以前的主题 独立研究了OOC的机电和流体稳态。通过结合这两个主题， 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的质量转运。 我们将使用三个结合物理和计算建模的目标检验该假设 方法。对于AIM 1，将使用活动物（Gerbil）的实验来表征声音和 质量（神经毒素）沿着耳蜗长度的质量（神经毒素）转运的外发细胞运动。 AIM 2实验 将使用植入新的微富集室中的出色的耳蜗组织来表征OOC蠕动 由于外发细胞运动性而引起的振动。对于AIM 3，新的生物物理计算机模型将模拟药物 沿着耳蜗的交付，从而整合了目标1和2的身体结果。 在美国，大约有五分之一的成年人有一定程度的听力损失。多种的 遗传性，与年龄相关和噪音引起的听力损失的常见形式被分配给故障 耳蜗流体稳态。通过从创新的角度调查耳蜗流体稳态 （机械师），该项目将提供一个解释，说明为什么高频声音更多 易受伤害的。从长远来看，我们有雄心提供一种补救措施，以延迟/防止与听力损失有关 液体群体。