Brain Prostheses: Promoting High Neuron Connectivity

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，并为大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神经元和假体设备上电极之间的高度连接。这样的连接将替换退行性疾病（例如帕金森病）中丢失的神经元，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，这将使我们能够测试我们的主要假设，即神经营养因子，例如神经生长因子（NGF）或脑源性神经营养因子（BDNF）可用于促进神经元发芽和直接过程生长到假体设备上的电极部位。化学工程和纳米纤维的原理将用于制造与缓释聚合物基质材料耦合的微机械装置，或用微流体通道制造，以控制生长因子直接释放到新皮层中。将使用定量方法来描述神经营养因子的时间和剂量依赖性梯度。神经科学家将通过描述和关联形态学和电生理学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，用于描述神经元突起的定向生长及其相对于假体器械上电极和生长因子释放位点的位置。将使用总电活动测量、单个单元分析和刺激研究来描述神经营养因子治疗对器械电极和靶神经元之间连接的影响。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修复装置。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.