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最常见的残疾。 人口对于听力损失太严重而无法通过助听器帮助的人，人工耳蜗植入已成为 护理标准。虽然它们可以恢复许多人理解语言的能力，但目前的电极 对神经元兴奋的选择性差。这限制了保真度，导致难以处理背景噪音， 电话和音乐欣赏。神经创伤、神经变性和神经退行性疾病中心的研究人员 CMC-VAMC的恢复（CNNR）开创了基于生物学的神经接口， 目前还没有应用于听力恢复的特定刺激。这个项目利用可移植的生命 通过生物混合神经接口进行听力康复的支架。 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 当它们的轴突与中枢听觉通路或耳蜗的神经元相互作用时， 从而形成“活性电极”。SGN将从新生大鼠颞骨中收获，并且细胞具有以下能力： 刺激SGN（耳蜗植入）和中枢衍生神经元（脑干）的不同群体 植入）将在培养中确认。光激活视蛋白也将被诱导以允许光激活。 刺激.然后将SGN在体外在两种不同的支架上生长。第一个引导移植的SGN轴突 到脑干的下丘，第二个引导他们从耳蜗的圆窗， 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 尸体一旦移植到活的大鼠中，用MTT法评估细胞存活和整合。 免疫组织化学在不同的时间点，长达6个月。听觉电生理记录 皮质将在植入脑干或耳蜗支架的退化大鼠中获得， 电刺激或光刺激。然后使用行为模型来评估听觉感知 通过对活支架的刺激来诱导。 该项目的最终产品将是两种用于听力康复的活体电极，一种用于 一个植入下丘，一个植入耳蜗。预计神经元- 这种技术所允许的特定模拟将允许精确地刺激听觉系统， 目前的植入技术无法达到。 这是一个新提案的重新提交。 这项工作是直接翻译为改善植入式听力设备为那些听力损失太多 助听器的选配方法有哪些？改善残疾人的康复选择 这些退伍军人将对他们的生活质量和福祉产生重大影响。 这项工作不仅推进了下一代基于生物学的界面， 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 这是一个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将构成 在推动听力恢复的界限的职业生涯的基础。

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.