Functional integration of elongated axon-electrode array constructs with the peri

细长轴突电极阵列结构与周围的功能集成

• 批准号: 8307690
• 负责人: HAN-CHIAO ISAAC CHEN
• 金额: $ 4.49万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307690
• 关键词: Action Potentials; Affect; American; Amputees; Axon; Biological; Biological Preservation; Brain; Cosmetics; Coupled; Data; Defect; Development; Electrodes; Electronics; Electrons; Elements; Engineering; Fluorescence; Foundations; Future; Generations; Growth; Hybrids; Immunohistochemistry; In Vitro; Indium; Individual; Infusion procedures; Injury; Length; Life; Limb structure; Link; Malignant Neoplasms; Maps; Measurement; Measures; Membrane; Methodology; Methods; Microelectrodes; Motor; Motor Cortex; Muscle; Natural regeneration; Nature; Nerve; Nervous system structure; Neuraxis; Neuroglia; Neurons; Outcome; Patients; Peripheral; Peripheral Nerves; Peripheral Nervous System; Plastic Embedding; Process; Productivity; Property; Prosthesis; Quality of life; Rattus; Research; Risk; Robotics; Scanning; Sensory; Signal Transduction; Site; Societies; Solid; Spinal Cord; Stretching; Synapses; Techniques; Technology; Tissues; Transplantation; Trauma; Ursidae Family; Vascular Diseases; Work; axon growth; axon regeneration; base; disability; emotional distress; experience; in vivo; innovation; microchip; novel; relating to nervous system; research study; robotic device; sciatic nerve; social; somatosensory; synaptogenesis; transmission process

DESCRIPTION (provided by applicant): Limb loss from vascular disease, trauma, and cancer currently affects nearly 2 million Americans. It is a devastating, life-altering condition for which no satisfactory treatment exists. A major obstacle in the creation of high-functioning neuroprosthetics is the lack of neural interfaces that efficiently convey both motor and sensory information between the host nervous system and peripheral robotic devices. The long-term objective of this project is the development of such an interface utilizing the peripheral nervous system as the site of interaction with a neuroprosthetic. This approach seeks to exploit the inherent processing power of the central nervous system and to minimize injury to healthy tissues that are accessed by existing interface technologies, such as brain and muscle. In order to create a novel neural interface based on the peripheral nervous system, this proposal employs a hybrid neuronal-electronic construct to connect with host neurons. This construct consists of mechanically elongated axonal tracts integrated with a microelectrode array. As opposed to the insertion of electrodes into peripheral nerves, the proposed strategy relies upon a biological interface with the host nervous system, which provides the significant advantage of long-term contact stability between the components of the interface. Two specific aims are targeted using the proposed hybrid-construct approach. First, the mechanisms of integration between the neuronal element of the hybrid construct and host neurons are explored. This integration is hypothesized to occur via either axon-guided regeneration of host axons or synaptic integration. Methods for differentiating these two possibilities include fluorescence immunohistochemistry for markers of axonal regeneration and synapse formation and direct measurements of host axonal growth. Second, the extent of functional integration between the hybrid construct and the host nervous system is investigated. The transmission of action potentials along the hybrid construct initially is examined in vitro. Subsequent in vivo studies assess the transmission of electrical activity to and from the host peripheral and central nervous systems, the latter involving motor cortex stimulation and mapping of somatosensory potential equivalents evoked by the microelectrode array. Techniques for enhancing functional integration may include the concurrent transplantation of glial cells and the infusion of trophic factors. Achieving the objectives of this project establishes the feasibility of a neural interface that interacts biologically with the peripheral nervous system. In the short-term, these results would provide the foundation for work to decode signals recorded by the hybrid-construct microelectrode array, which could then be used to drive simple robotic tasks. Long-term, successful completion of this project would create a new avenue for research into a viable neural interface with advanced neuroprosthetics.

描述(由申请人提供)： 血管疾病、创伤和癌症导致的肢体丧失目前影响着近200万美国人。这是一种毁灭性的、改变生活的疾病，目前还没有令人满意的治疗方法。创造高功能神经假体的一个主要障碍是缺乏在宿主神经系统和外围机器人设备之间有效传递运动和感觉信息的神经接口。该项目的长期目标是开发这样一种接口，利用周围神经系统作为与神经假体相互作用的场所。这种方法寻求利用中枢神经系统固有的处理能力，并将对现有接口技术访问的健康组织(如大脑和肌肉)的损害降至最低。为了创造一种新的基于周围神经系统的神经接口，该方案采用了神经元-电子混合结构来连接宿主神经元。这种结构由机械拉长的轴索和微电极阵列组成。与将电极插入周围神经不同，所提出的策略依赖于与宿主神经系统的生物接口，这提供了接口组件之间长期接触稳定的显著优势。使用拟议的混合构造方法针对两个具体目标。首先，探索了混合构建的神经元元件与宿主神经元之间的整合机制。这种整合被认为是通过轴突引导的宿主轴突再生或突触整合发生的。区分这两种可能性的方法包括轴突再生和突触形成的标记的荧光免疫组织化学和直接测量宿主轴突生长。其次，研究了杂合结构和宿主神经系统之间的功能整合程度。最初在体外检测了动作电位沿杂交结构的传递。随后的活体研究评估了电活动传入和传出宿主周围和中枢神经系统的情况，后者涉及运动皮质刺激和微电极阵列诱发的体感电位等价物的标测。增强功能整合的技术可能包括同时移植神经胶质细胞和注入营养因子。实现这一项目的目标，建立了一种与周围神经系统进行生物互动的神经接口的可行性。在短期内，这些结果将为解码混合结构微电极阵列记录的信号提供基础，然后可以用来驱动简单的机器人任务。该项目的长期成功完成将为研究具有先进神经假体的可行神经接口开辟一条新的途径。