Mechanisms of Oligodendrocyte Activity on Chronic Brain Implants and Recording Performance

少突胶质细胞活性对慢性脑植入物和记录性能的机制

• 批准号: 10734458
• 负责人: FRANCA CAMBI
• 金额: $ 60.97万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734458
• 关键词: Affect; Aneurysm; Astrocytes; Autopsy; Axon; Basic Science; Blood - brain barrier anatomy; Blood flow; Brain; Brain Injuries; Calcium; Cells; Chronic; Cicatrix; Clinical; Clinical Sciences; Cuprizone; Data; Demyelinations; Devices; Electrodes; Electrophysiology (science); Encapsulated; Engineering; Failure; Foreign Bodies; Gene Expression Profiling; Health; Hemorrhage; Hippocampus; Histology; Human; Imaging technology; Impairment; Implant; Individual; Inflammatory; Injury; Intervention; Ischemia; Knowledge; Lead; Mechanics; Metabolic; Methods; Microelectrodes; Microglia; Molecular; Molecular Target; Motor; Motor Cortex; Mus; Muscarinic Acetylcholine Receptor; Myelin; Nerve Degeneration; Neurodegenerative Disorders; Neuroglia; Neurons; Neurosciences; Oligodendroglia; Outcome; Output; Penetration; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacological Treatment; Physiology; Play; Process; Publishing; Recovery of Function; Reporter; Role; Site; Source; Stroke; System; Technology; Testing; Time; Tissues; Toxin; Transgenic Animals; Transgenic Organisms; Translations; Traumatic Brain Injury; Universities; Visual; Visual Cortex; Work; antagonist; brain computer interface; cell type; cost; density; design; flexibility; functional restoration; implantation; improved; in vivo; in vivo imaging; injury recovery; innovation; multiphoton imaging; multiphoton microscopy; myelination; nervous system disorder; neural; neural implant; neural network; neural stimulation; neuron loss; neuroprosthesis; neuroprotection; novel; oligodendrocyte progenitor; pharmacologic; remyelination; response; stem cells; ultrasound; wireless

Project Summary This R01 (PA-20-185) application aims to greatly improve basic science understanding of oligodendrocytes with respect to spatial and temporal dynamic changes around chronically implanted microelectrodes and long- term recording performance. Penetrating recording microelectrode arrays are a crucial component of numerous human neuroprosthetics. Obtaining selective, high fidelity, long-lasting readouts of brain activity is a critical technology across basic and applied neuroscience that impacts motor, pre-motor, and visual cortex neuroprostheses and brain-computer interfaces. However, implantation of cortical microelectrodes causes a reactive tissue response, which results in a degradation of the preferred functional single-unit performance over time, thus limiting the device capabilities. While the BBB and the role of other glial cells like microglia and astrocytes have long been studied with respect to the degradation of chronic recording performance, the role of oligodendrocytes and oligodendrocyte progenitor in this foreign body response has been understudied. This proposal aims to characterize the role of oligodendrocytes and chronic recording failure in vivo caused by the insertion via quantifying structural, cellular, and molecular level tissue response to chronic implants in the brain in real time through combining multiphoton imaging technology and neural engineering technology at the University of Pittsburgh. A dynamic understanding of the interfaces is necessary for elucidating the mechanism(s) behind neural recording failure. Oligodendrocytes and oligodendrocyte progenitor cells have been implicated as key players in neuronal health following brain injury and numerous neurodegenerative diseases. Therefore, we will utilize transgenic animals with specific activity indicators in oligodendrocytes as well as pharmaceutical and gliomodulation approaches that target oligodendrocytes in order to explore mechanisms that improve oligodendrocyte health and chronic intracortical recording performance. This work has the potential to output basic and clinical science level knowledge relevant to neural engineering, ischemia, stroke, intracortical hemorrhage, aneurysm, traumatic brain injury, MS, ALS, and closed-loop neurostimulation.

项目摘要 R01(PA-20-185)的应用旨在极大地提高对少突胶质细胞的基础科学理解 对于长期植入的微电极和长时间电极周围的空间和时间动态变化。 学期录音表现。穿透式记录微电极阵列是 无数的人类神经假体。获得选择性、高保真、持久的大脑活动读数是一种 跨越基础神经科学和应用神经科学的关键技术，影响运动、运动前和视觉皮质 神经假体和脑机接口。然而，皮质微电极的植入会导致 反应性组织反应，导致首选的功能单一单元性能下降 随着时间的推移，从而限制了设备的能力。而血脑屏障和其他胶质细胞的作用，如小胶质细胞和 长期以来，关于星形胶质细胞在慢性记录性能退化方面的作用已有研究 少突胶质细胞和少突胶质前体细胞在这种异物反应中的研究还不够深入。 这项建议旨在表征少突胶质细胞在体内引起的慢性记录失败的作用 通过量化结构、细胞和分子水平的组织对慢性种植体的反应来插入 通过将多光子成像技术和神经工程技术相结合，实时检测大脑 匹兹堡大学。对界面的动态理解对于阐明 神经记录失败背后的机制(S)。少突胶质细胞和少突胶质祖细胞 被认为是脑损伤和大量神经退行性变后神经元健康的关键因素 疾病。因此，我们将利用在少突胶质细胞中具有特定活性指标的转基因动物作为 以及针对少突胶质细胞的药物和胶质调节方法，以探索 改善少突胶质细胞健康和慢性皮质内记录性能的机制。这部作品 有潜力输出基础和临床科学水平的有关神经工程，缺血， 中风、皮质内出血、动脉瘤、创伤性脑损伤、多发性硬化症、肌萎缩侧索硬化症和闭合式神经刺激。