Living electrodes for auditory rehabilitation.

用于听觉康复的活体电极。

• 批准号: 10618167
• 负责人: Jason Brant
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618167
• 关键词: Acoustic Stimulation; Affect; American; Auditory; Auditory Perception; Auditory area; Auditory system; Axon; Behavioral; Behavioral Model; Biological; Brain; Brain Stem; Cell Survival; Cells; Clinical; Cochlea; Cochlear Implants; Cochlear implant procedure; Cochlear nucleus; Custom; Electric Stimulation; Electrodes; Electrophysiology (science); Environment; Evaluation; Foundations; Geographic Locations; Harvest; Hearing; Hearing Aids; Immunohistochemistry; Implant; In Vitro; Inferior; Inferior Colliculus; Job Description; K-Series Research Career Programs; Length; Light; Lipreading; Measurable; Microelectrodes; Music; Neonatal; Nerve Degeneration; Nerve Regeneration; Nervous System Trauma; Neurons; Noise; Opsin; Optics; Patients; Peripheral; Personal Satisfaction; Persons; Phenotype; Population; Quality of life; Rattus; Rehabilitation therapy; Research Personnel; Residual state; Risk; Services; Signal Transduction; Specificity; Speech; Synapses; Technical Expertise; Techniques; Technology; Telephone; Temporal bone structure; Testing; Thinking; Tinnitus; Tissue Engineering; Transplantation; Veterans; Work; auditory nuclei; auditory pathway; auditory rehabilitation; base; career; deaf; design; design and construction; disability; efficacy evaluation; ganglion cell; hearing impairment; hearing restoration; implant design; implantation; improved; in vivo; microstimulation; military veteran; multi-electrode arrays; neural; neuronal cell body; next generation; normal hearing; novel; optogenetics; regenerative therapy; restoration; round window; scaffold; signal processing; simulation; spiral ganglion; standard of care; synaptogenesis

Hearing loss affects over 28 million Americans and is the second most common disability in the Veteran population. For hearing loss too severe to be helped by hearing aids, cochlear implants have become the standard of care. Though they can restore the ability to understand speech for many, current electrodes have poor selectivity for neuronal excitation. This limits fidelity leading to difficulty with background noise, talking on the phone, and music appreciation. Researchers at the Center for Neurotrauma, Neurodegeneration, and Restoration (CNNR) at the CMC-VAMC have pioneered biologically-based neural interfaces with neuron- specific stimulation that have yet to be applied to hearing restoration. This project utilizes transplantable living scaffolds for the rehabilitation of hearing through biohybrid neural interfaces. Biohybrid neural interfaces will be developed that allow transplanted spiral ganglion neurons (SGN) to remain accessible to stimulation while their axons interact with neurons of the central auditory pathway or cochlea – creating a “living electrode”. SGN will be harvested from neonatal rat temporal bones and the cells’ ability to stimulate a distinct population of SGN (cochlear implantation), and centrally derived neurons (brainstem implantation) will be confirmed in culture. Light activated opsins will also be induced to allow for optical stimulation. SGNs will then be grown on two distinct scaffolds in vitro. The first directs transplanted SGN axons to the inferior colliculus in the brainstem, and the second directs them from the round window of the cochlea to the native spiral ganglion. Both designs allow for electric and optical stimulation of the transplanted SGN cell bodies. Once transplanted into living rats, cell survival and integration are evaluated with immunohistochemistry at various timepoints for up to 6 months. Electrophysiologic recordings from the auditory cortex will be obtained in deafened rats implanted with either the brainstem or cochlear scaffolds, while being stimulated either electrically or optically. Behavioral models will then used to evaluate the auditory perception induced via stimulation of the living scaffolds. The final product of this project will be two form-factors of living electrodes for hearing rehabilitation, one for implantation into the inferior colliculus and one for implantation into the cochlea. It is expected that the neuron- specific simulation permitted by this technique will allow for precision in stimulation of the auditory system that cannot be approached by current implant technology. This is a resubmission of a new proposal. This work is directly translatable to improved implantable hearing devices for those with hearing loss too severe to be adequately rehabilitated with traditional hearing aids. Improvement in the rehabilitative options for these veterans will have a significant impact on their quality of life and well-being. Not only does the proposed work advance a next generation, biologically based interface to restore the ability to interpret sophisticated auditory inputs in our Veterans, as a Career Development Award, it will also serve as vehicle to expand my technical skills in tissue engineering and regenerative therapies. This CDA will form the foundation of a career in pushing the boundaries of hearing restoration.

听力损失影响着超过 2800 万美国人，是退伍军人中第二大常见的残疾 人口。对于听力损失严重而无法通过助听器帮助的情况，人工耳蜗已成为解决问题的方法。 护理标准。虽然它们可以恢复许多人理解语音的能力，但目前的电极已经 神经元兴奋的选择性较差。这限制了保真度，导致背景噪音困难，继续交谈 电话、音乐欣赏。神经创伤、神经变性中心的研究人员 CMC-VAMC 的恢复 (CNNR) 开创了基于生物的神经元接口 尚未应用于听力恢复的特定刺激。该项目利用可移植的活体 通过生物混合神经接口康复听力的支架。 将开发生物混合神经接口，允许移植的螺旋神经节神经元（SGN）保留 当它们的轴突与中央听觉通路或耳蜗的神经元相互作用时，可以接受刺激—— 创造“活电极”。 SGN 将从新生大鼠颞骨中采集，这些细胞具有 刺激独特的 SGN（人工耳蜗植入）群体和中枢衍生神经元（脑干） 植入）将在培养中得到证实。光激活视蛋白也将被诱导以允许光学 刺激。然后，SGN 将在体外在两个不同的支架上生长。第一个指导移植的 SGN 轴突 到脑干的下丘，第二个将它们从耳蜗的圆窗引导到 原生螺旋神经节。两种设计都允许对移植的 SGN 细胞进行电刺激和光刺激 尸体。一旦移植到活体大鼠中，就可以用以下方法评估细胞存活和整合： 在长达 6 个月的不同时间点进行免疫组织化学分析。听觉电生理记录 皮层将在植入脑干或耳蜗支架的聋鼠身上获得，同时 电或光刺激。然后将使用行为模型来评估听觉感知 通过刺激活支架诱导。 该项目的最终产品将是两种形状因数的用于听力康复的活体电极，一种用于听力康复 一种用于植入下丘，另一种用于植入耳蜗。预计神经元 该技术允许的特定模拟将允许精确刺激听觉系统， 目前的植入技术无法实现这一点。 这是重新提交新提案。 这项工作也可以直接转化为针对听力损失患者的改进的植入式听力设备 严重者可使用传统助听器进行充分康复。改善康复选择 这些退伍军人将对他们的生活质量和福祉产生重大影响。 拟议的工作不仅推进了下一代基于生物学的界面来恢复能力 解释我们退伍军人复杂的听觉输入，作为职业发展奖，它也将作为 扩展我在组织工程和再生疗法方面的技术技能的工具。该 CDA 将组成 为推动听力恢复界限的职业生涯奠定了基础。

项目成果

Signal processing and stimulation potential within the ascending auditory pathway: a review.

• DOI: 10.3389/fnins.2023.1277627
• 发表时间: 2023
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Quimby, Alexandra E.;Wei, Kimberly;Adewole, Dayo;Eliades, Steven;Cullen, D. Kacy;Brant, Jason A.
• 通讯作者: Brant, Jason A.