Brain Prostheses: Promoting High Neuron Connectivity

描述(由申请人提供)： 神经假体设备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。我们的长期目标之一是通过控制神经假体设备周围的细胞反应来改善这些设备的功能。这项提议的主要焦点是促进假体设备上神经元和电极之间的高连接性。这种连接将取代退行性疾病(如帕金森氏病)中丢失的神经元，或控制病理事件，如癫痫，或在脑损伤后提供必要的大脑输入/输出，如中风或创伤。我们建议使用多学科方法来设计和制造设备，使我们能够测试我们的主要假设，即神经营养因子，如神经生长因子(NGF)或脑源性神经营养因子(BDNF)可用于促进神经元萌发，并将突起生长定向到假体设备上的电极位置。化学工程和纳米制造的原理将被用来制造与缓释聚合物基质材料耦合的微机械装置，或者利用微流控通道来控制生长因子直接释放到新皮质。定量方法将被用来描述神经营养因子的时间和剂量依赖的梯度。神经学家将通过描述和关联形态和电生理测量来评估神经元的反应。组织化学方法、直接神经元填充和图像分析技术描述神经元突起的定向生长及其相对于假体设备上电极和生长因子释放部位的位置。总电活动的测量、单单位分析和刺激研究将被用来描述神经营养素治疗对装置电极和靶神经元之间连接的影响。这些实验结果将为设计新一代功能动态微机械假肢装置提供制造策略。这些设备将为神经元提供高传导性的长期功能连接，确保它们在慢性治疗和大脑研究中的使用。

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.