Mechanisms of Brain Tissue Response to Implanted Devices

描述(由申请人提供)： 我们将研究长期植入的生物医学设备性能下降的原因。微电极阵列将被植入成年大鼠的听觉皮质。将进行电生理记录，以测量电极阻抗并记录诱发的单单位活动。植入后3至28天处死动物，应用免疫组织化学方法。将对回收的微电极上的吸附电池类型进行评估。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是如何导致记录电极的单单位记录的阻抗增加和损失的。(2)微电极的阻抗将根据吸附物种的可用性在体外进行表征。在基线鉴定后，细胞外分子将被添加到包括蛋白质和细胞(反应性小胶质细胞、星形胶质细胞和成纤维细胞)的培养液中，并且鉴定将继续进行。培养物将在不同的时间固定，并使用间接免疫组织化学和细胞类型特异性标记进行检测。阻抗的变化将与吸附物种和细胞定植的程度相关。(3)将混合原代细胞悬浮在细胞外基质凝胶中，建立静息的脑组织三维培养模型。经血清处理的探针将被植入，并使用显微镜方法和间接免疫组织化学方法评估反应。将评估检测小胶质细胞激活的顺序变化的能力。这个项目的长期目标是制定治疗异常的方法，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.