Brain Prostheses: Promoting High Neuron Connectivity

神经假体装置为治疗人类疾病提供了巨大的希望，并为长期的疾病提供了方法。 大脑神经元的长期研究。我们的长期目标之一是改善神经假体的功能 通过控制这些设备周围的细胞反应来发展。本提案的主要重点是 促进神经元和假体装置上的电极之间的高度连接。这种连接将 替代退行性疾病中丢失的神经元，例如Parksionson病，或控制病理事件，例如 癫痫，或在脑损伤（例如中风或创伤）后提供必要的脑输入/输出。我们建议 使用多学科的方法来设计和制造设备，使我们能够测试我们的原则， 假设神经营养因子，例如神经生长因子（NGF）或脑源性神经营养因子 脑源性神经营养因子（BDNF）可促进神经元发芽，并将突起生长导向假体上的电极部位 装置.化学工程和纳米纤维的原理将用于制造微机械 耦合到缓释聚合物基质材料或用微流体通道制造的装置， 生长因子直接释放到新皮层。将使用定量方法来描述时间和 神经营养因子的剂量依赖性梯度。神经科学家将通过描述和 将形态学和电泳学测量相关联。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及其位置的定向生长 相对于假体装置上的电极和生长因子释放位点。总电气测量 活性、单单位分析和刺激研究将被用来描述神经营养因子的作用 治疗设备电极和目标神经元之间的连接。这些实验的结果 将提供制造策略，以设计新一代的功能动态微机械 假肢装置这些器件将提供高导电性的长期功能连接， 神经元，确保它们在慢性治疗和大脑研究中的使用。

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 imporving the function of neural prosthetic devbies 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. Parksionson'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 grwoth 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 electrophsyiological measurements. Histochemical methods, direct neuron filling, nad image analysis techniques tod escribe directed grwoth of neuron processes and their postions relative to electrode and grwoth factor release sites on prosthetic devices. Measurements of total electrical activity, single unit analysis, and stimulation studies willbe 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.