Mechanisms behind Electrode Induced BBB damage's impact on neural recording

 描述（由申请人提供）：穿透记录微电极阵列是许多人类神经假体的关键组成部分。 获得大脑活动的选择性，高保真度，持久的读数是基础和应用神经科学的关键技术，影响学习和记忆研究以及运动，运动前和视觉皮层神经假体和脑机接口。 然而，植入皮质微电极会引起反应性组织反应，导致首选功能性单单元性能随时间推移而退化，从而限制了器械性能。 神经探针或微电极的插入不可避免地破坏血脑屏障（BBB）的完整性，并导致微血管扩张，这已被证明会触发炎症组织反应级联反应。 探针插入导致的微血管化程度已被证明是不可控制的，并且难以在植入物中重现，反映了炎症组织反应和长期记录成功率的巨大差异。 我们假设血脑屏障损伤的水平影响慢性神经记录质量。 该提案旨在通过结合匹兹堡大学的多光子成像技术和神经工程技术，在真实的时间内量化对脑中慢性植入物的结构、细胞和分子水平组织反应，来表征由插入诱导的BBB破坏和BBB闭塞引起的体内持续BBB破坏和慢性记录失败。 动态的接口的理解是必要的阐明神经记录失败背后的机制。 这项工作有可能输出与神经工程，缺血，中风，皮质内出血，动脉瘤，创伤性脑损伤和闭环神经刺激相关的基础和临床科学水平的知识。

 DESCRIPTION (provided by applicant): 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 learning and memory studies as well as 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. Insertion of neural probes or microelectrodes inevitably disrupts the blood-brain barrier (BBB) integrity and causes microhemorrhages that have been shown to trigger the inflammatory tissue response cascade. The degree of microhemorrhaging from probe insertion has been shown to be uncontrollable and difficult to reproduce across implants, mirroring the large variability in inflammatory tissue responses and chronic recording success. We hypothesize that the level of BBB damage impacts chronic neural recording quality. This proposal aims to characterize the sustained BBB breakdown and chronic recording failure in vivo caused by the insertion induced BBB disruption and BBB occlusion by 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. 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, and closed-loop neurostimulation.