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

 描述(申请人提供)：穿透式记录微电极阵列是许多人类神经假体的重要组成部分。获得选择性、高保真、持久的大脑活动读数是基础和应用神经科学中的一项关键技术，它影响学习和记忆研究以及运动、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引起组织的反应性反应，这会导致首选的功能单位性能随着时间的推移而退化，从而限制了设备的能力。神经探头或微电极的插入不可避免地破坏血脑屏障(BBB)的完整性，并导致微小出血，已被证明触发炎症组织反应级联反应。探针插入造成的微出血程度已被证明是不可控制的，很难在植入物之间复制，这反映了炎症组织反应和慢性记录成功的巨大变异性。我们假设血脑屏障损伤的程度影响慢性神经记录的质量。这项建议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，实时定量组织对脑内慢性植入物的结构、细胞和分子水平的反应，来表征由插入引起的血脑屏障中断和血脑屏障闭塞导致的体内持续的血脑屏障破坏和慢性记录失败。为了阐明神经记录失败背后的机制(S)，动态地理解这些界面是必要的。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、创伤性脑损伤和闭合式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.