Brain Prostheses: Promoting High Neuron Connectivity

大脑假体：促进神经元的高连接性

• 批准号: 6906447
• 负责人: William G Shain
• 金额: $ 52.6万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6906447
• 关键词: SDS polyacrylamide gel electrophoresis; autoradiography; axon; brain; brain derived neurotrophic factor; calorimetry; dendrites; enzyme linked immunosorbent assay; immunocytochemistry; infrared spectrometry; laboratory rat; neocortex; nerve growth factors; nervous system prosthesis; neuronal guidance; neurons; neurophysiology; neurotrophic factors; scanning electron microscopy; tissue /cell culture

DESCRIPTION (provided by applicant): Neural prosthetic devices offer great promise for treating human disease and providing methods for the long-term study of brain neurons. One of our long-range goals is improving the function of neural prosthetic devices by controlling cellular responses around these devices. The primary focus of this proposal is the promotion of high connectivity between neurons and electrodes on prosthetic devices. Such connectivity will replace lost neurons in degenerative disease, e.g. Parkinson's disease, or control pathologic events, e.g. epilepsy, or provide necessary brain input/output following brain injury, e.g. stroke or trauma. We propose to use a multidisciplinary approach to design and fabricate devices that will allow us to test our principal hypothesis that neurotrophic factors, e.g. nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) can be used to promote neuron sprouting and direct process growth to electrode sites on prosthetic devices. Principles of chemical engineering and nanofabrication will be used to fabricate micro-machined devices coupled to slow-release polymer matrix materials or fabricated with microfluidic channels to control release of growth factors directly into neocortex. Quantitative methods will be used to describe time- and dose-dependent gradients of neurotrophins. Neuroscientists will assess neuron responses by describing and correlating morphological and electrophysiological measurements. Histochemical methods, direct neuron filling, and image analysis techniques to describe directed growth of neuron processes and their positions relative to electrode and growth factor release sites on prosthetic devices. Measurements of total electrical activity, single unit analysis, and stimulation studies will be used to describe the effects of neurotrophin treatment on connectivity between device electrodes and target neurons. Results from these experiments will provide fabrication strategies to design a new generation of functionally dynamic micro-machined prosthetic devices. These devices will provide highly conductive, long-term functional connections to neurons, insuring their use in chronic treatment and studies of the brain.

描述（由申请人提供）： 神经假体装置为治疗人类疾病提供了巨大的希望，并为脑神经元的长期研究提供了方法。我们的远程目标之一是通过控制这些设备周围的细胞反应来改善神经假体设备的功能。该提案的主要重点是促进假体设备上神经元和电极之间的高连通性。这种连通性将取代退行性疾病中失去的神经元，例如帕金森氏病或控制病理事件，例如癫痫病，或在脑损伤后提供必要的大脑输入/输出，例如中风或创伤。我们建议使用多学科方法设计和制造设备，以使我们能够检验我们的主要假设，即神经营养因素，例如神经生长因子（NGF）或脑衍生的神经营养因子（BDNF）可用于促进神经元的发芽，并将过程生长直接到假体设备上的电极位点。化学工程原理和纳米化的原理将用于制造与缓慢释放的聚合物基质材料或用微流体通道制造的微型机械设备，以控制直接释放生长因子到新皮层中。定量方法将用于描述神经营养蛋白的时间和剂量依赖性梯度。神经科学家将通过描述和相关的形态学和电生理测量来评估神经元反应。组织化学方法，直接神经元填充和图像分析技术，以描述神经元过程的定向生长及其位置相对于假体设备上的电极和生长因子释放位点。总电活动，单个单位分析和刺激研究的测量将用于描述神经营养蛋白治疗对装置电极和靶神经元之间连通性的影响。这些实验的结果将提供制造策略，以设计新一代功能动态的微型固定设备。这些设备将为神经元提供高度导电的长期功能连接，从而确保其在慢性治疗和大脑研究中的使用。