Mechanisms of Brain Tissue Response to Implanted Devices

描述（由申请人提供）： 慢性植入的生物医学设备的性能下降的机制将进行调查。将微电极阵列植入成年大鼠的听觉皮层。将进行电生理记录，以测量电极阻抗并记录诱发的单个单位活动。在植入后3 - 28天处死动物，并应用免疫组织化学方法。将评价回收微电极上吸附的细胞类型。电阻抗和记录活动的变化将与组织反应相关。目的是确定小胶质细胞和星形胶质细胞成分如何有助于增加电阻抗和记录电极的单个单位记录的损失。(2)微电极的阻抗将基于吸附物质的可用性在体外表征。在基线表征后，将细胞外分子添加到培养基中，包括蛋白质和细胞（反应性小胶质细胞、星形胶质细胞和成纤维细胞），并继续表征。将在不同时间固定培养物，并使用间接免疫组织化学和细胞类型特异性标志物进行检查。阻抗的变化将与吸附物种和细胞定殖的程度相关。(3)将使用悬浮在细胞外基质凝胶中的混合原代细胞创建皮质脑组织的静息3-D培养模型。将植入经血清处理的探针，并使用显微镜方法和间接免疫组织化学评价反应。将评价检测小胶质细胞活化的顺序变化的能力。该项目的长期目标是制定异常的方法，并更好地了解大脑中的伤口愈合反应。

DESCRIPTION (provided by applicant): The mechanisms underlying decreased performance of chronically implanted biomedical devices will be investigated. Microelectrode arrays will be implanted into the auditory cortex of adult rats. Electrophysiological recordings will be performed to measure electrode impedance and record evoked single unit activity. Animals will be sacrificed from 3 to 28 days post-implant and immunohistochemical methods applied. The adsorbed cell types on retrieved microelectrodes will be evaluated. Changes in electrical impedance and recording activity will be correlated with tissue response. The objective is to determine how microglial ceils and astrocytic components contribute to increasing electrical impedance and loss of single unit recording with recording electrodes. (2) The impedance of microelectrodes will be characterized in vitro based on adsorbing species availability. After baseline characterization, extracellular molecules will be added to the media including proteins and ceils (reactive microglia, astrocytes, and fibroblasts) and characterization will continue. Cultures will be fixed at various times and examined using indirect immunohistochemistry and cell type specific markers. Changes in impedance will be correlated with adsorbing species and the extent of cell colonization. (3) A resting 3-D culture model of cortical brain tissue will be created using mixed primary cells suspended in an extracellular matrix gel. Serum treated probes will be implanted, and the response evaluated using microscopic methods and indirect immunohistochemistry. The ability to detect sequential changes in microglial activation will be evaluated. The long-term objective of this project is to formulate approaches to abnormality and to better understand the wound healing response in brain.