Prolonged Local Melatonin Delivery for Recurrent Laryngeal Nerve Neuropraxia

延长局部褪黑激素递送治疗喉返神经神经失用症

• 批准号: 10513832
• 负责人: Ashley Kita
• 金额: $ 20.19万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10513832
• 关键词: Acids; Action Potentials; Affect; Anesthesia procedures; Animal Model; Award; Axon; Biomedical Engineering; Biostatistical Methods; Breathing; Cell Proliferation; Cells; Cellular Morphology; Clip; Communication; Complication; Counseling; Crush Injury; Data; Data Analyses; Deglutition; Demyelinations; Development; Development Plans; Diameter; Drug Delivery Systems; Dysphonia; Electromyography; Encapsulated; Exhibits; Exposure to; Fibrin; Fibrinogen; Funding; Glycolates; Goals; Grant; Head and Neck Surgeon; Head and Neck Surgery; Hydrogels; Image; Immunohistochemistry; Impairment; Implant; In Vitro; Individual; Inflammation; Injections; Injury; Intervention; Ipsilateral; K-Series Research Career Programs; Knowledge; Laryngeal muscle structure; Laryngoscopy; Larynx; Left; Long-Evans Rats; Measurement; Measures; Mechanics; Melatonin; Melatonin Receptors; Mentors; Mentorship; Methods; Modeling; Monaco; Monitor; Morphology; Motion; Movement; Nature; Neck; Nerve; Neural Conduction; Neuromuscular Junction; Neurosciences; Operative Surgical Procedures; Otolaryngology; Oxidative Stress; Oxygen Consumption; Patients; Peripheral Nerves; Peripheral nerve injury; Pharmaceutical Preparations; Postoperative Period; Procedures; Proliferating; Quality of life; Rattus; Recovery; Recovery of Function; Recurrence; Recurrent Laryngeal Nerve; Request for Applications; Research; Research Design; Risk; Schwann Cells; Severities; Site; Spectrophotometry; Speech; Stains; System; Therapeutic; Thrombin; Thyroidectomy; Time; Topical application; Trauma; Tuna; Ultrasonography; United States National Institutes of Health; Up-Regulation; Visualization; Voice; Work; aspirate; career development; collaborative environment; culture plates; design; improved; injured; injury recovery; insight; interest; meter; mitochondrial dysfunction; nerve injury; particle; preservation; remyelination; response; scaffold; screening; skills; therapeutic evaluation; timeline; tissue culture; translational scientist; vocal cord

Project Summary/Abstract: This application requests a career development award for a head and neck surgeon with an interest in recurrent laryngeal nerve neuropraxia and developing prolonged methods of topical therapeutic delivery. The described career development plan will help her to build the skills in data analysis, study design, and drug delivery necessary to become an independent translational researcher developing topical therapeutics for Otolaryngology applications. The candidate’s mentorship team combines expertise from neuroscience, bioengineering, laryngology, and otolaryngology to provide a collaborative environment to help her accomplish her goals. Dr. Kita’s objectives during this mentored career development award will be: 1) Complete coursework in biostatistical methods, 2) Develop expertise in sustained-release therapeutics, and 3) Design a method of further characterizing recovery from neuropraxia in a Long Evans rat model. Manipulation of the recurrent laryngeal nerve is common in surgical procedures of the neck. Postoperative weakness can results in difficulty with speech, swallowing, and breathing. Return of function from neuropraxia, the mildest and most common form of nerve injury, often takes a few months. The impairment in communication, swallowing ability, and breathing that results can severely impact patient quality of life during this time. This award will allow the candidate to study recovery from neuropraxia and screen topical interventions for their ability to expedite recovery. Through the completion of this award, Dr. Kita will establish preliminary data and a model of neuropraxia that may be used to test therapeutics. This will be accomplished in 3 aims: 1. Design a drug-eluting hydrogel with sustained elution. Melatonin will be encapsulated in poly (lactic-co- glycolic acid) microparticles within fibrin hydrogels and elution of medication characterized. 2. Determine Schwann cell response to melatonin in vitro. Schwann cells will be grown with resuspended melatonin, filter-sterilized eluted melatonin, and with melatonin secreted from microparticles in hydrogels. 3. Create a rat model for characterizing recovery from recurrent laryngeal nerve after neuropraxia. Vocal fold movement video, electromyography readings, ultrasonography, and immunohistochemistry will be used to describe recovery after injury in a Long-Evans rat model. Drug-eluting hydrogels will be implanted and analyzed for their ability to shorten the period to recovery of vocal fold motion seen on ultrasonography. Recurrent laryngeal nerve neuropraxia is a common and debilitating complication after surgeries in the neck. Better characterization of this injury will allow insight into ways to help at risk individuals. Through this award the candidate will investigate a method of prolonged topical therapeutic delivery for its ability to assist in recovery of vocal fold function after surgical manipulation and establish the skills necessary to become an independent translational researcher.

项目摘要/摘要： 此申请要求为有兴趣的头颈外科医生提供职业发展奖 喉返神经神经失用和开发长期局部治疗递送方法。这 所描述的职业发展计划将帮助她培养数据分析、研究设计和药物方面的技能 成为一名独立的转化研究人员开发局部疗法所必需的交付 耳鼻喉科应用。候选人的导师团队结合了神经科学的专业知识， 生物工程、喉科和耳鼻喉科提供协作环境来帮助她完成任务 她的目标。 Kita 博士在获得指导的职业发展奖期间的目标是： 1) 完成课程作业 生物统计方法，2) 发展缓释疗法方面的专业知识，以及 3) 设计一种方法 进一步表征了 Long Evans 大鼠模型中神经失用的恢复。 喉返神经的操作在颈部外科手术中很常见。 术后虚弱可能导致言语、吞咽和呼吸困难。函数的返回值来自 神经失用是最轻微和最常见的神经损伤形式，通常需要几个月的时间。减值 沟通、吞咽能力和呼吸可能会严重影响患者的生活质量 这次。该奖项将允许候选人研究神经失用症的恢复并筛选局部干预措施 因为他们有能力加速康复。通过完成该奖项，Kita 博士将建立初步数据 以及可用于测试治疗的神经失用模型。这将通过三个目标来实现： 1. 设计具有持续洗脱功能的药物洗脱水凝胶。褪黑激素将被封装在聚（乳酸-co- 乙醇酸）纤维蛋白水凝胶内的微粒和药物的洗脱特征。 2. 体外确定雪旺细胞对褪黑激素的反应。雪旺细胞将在重悬的情况下生长 褪黑激素、过滤灭菌的洗脱褪黑激素以及从水凝胶中的微粒分泌的褪黑激素。 3. 创建大鼠模型，用于表征神经失用后喉返神经的恢复。声乐 折叠运动视频、肌电图读数、超声检查和免疫组织化学将用于 描述 Long-Evans 大鼠模型受伤后的恢复情况。药物洗脱水凝胶将被植入并进行分析 因为它们能够缩短超声检查中看到的声带运动恢复的时间。 喉返神经神经失用是喉返神经手术后常见且使人衰弱的并发症。 脖子。更好地描述这种伤害将有助于深入了解帮助高危人群的方法。通过这个 获奖者将研究一种延长局部治疗递送的方法，因为它能够协助 手术操作后声带功能的恢复，并建立成为一名声乐家所需的技能 独立翻译研究员。