CNS Response to Implanted Materials

中枢神经系统对植入材料的反应

• 批准号: 7157609
• 负责人: Patrick A Tresco
• 金额: $ 32.78万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157609
• 关键词: CNS; Response; Implanted; Materials

DESCRIPTION (provided by applicant): Implantable silicon microelectrode array technology is a promising approach for high-density, high-resolution sampling of neuronal activity with application in both basic research and prosthetic devices. One of the major limitations of the current technology is inconsistent performance in long-term applications, which limits clinical development. Although the brain tissue response to implanted electrodes is believed to be a major cause of electrical instability, the precise mechanisms that cause failure of recordings are not known. Understanding the mechanisms that underlie chronic instability of silicon microelectrode arrays will, therefore, lead to strategies to improve their usefulness for chronic basic science studies and various neuroprosthetic applications. We have observed persistent ED-1 immunoreactivity around silicon microelectrode arrays implanted in the adult rat motor cortex, and observed significant reductions in nerve fiber density and cell bodies in the tissue immediately surrounding implanted silicon microelectrode arrays. Persistent ED-1 up-regulation and neurodegeneration is not observed in microelectrode stab controls indicating that chronic inflammation and neuronal loss is not caused by the initial mechanical trauma of electrode implantation, but is associated with the brain tissue response to the implanted electrode. We find that our observations share biological features of diseases having a neuroinflammatory mediated neurotoxic component. We, therefore, hypothesize that chronically implanted silicon microelectrode arrays lead to persistent macrophage activation at the microelectrode interface resulting in an over production of proinflammatory cytokines and neurotoxic factors that lead to loss of neuronal cell bodies and fibers immediately adjacent to the recording surface. To test our hypothesis, quantitative methods are proposed: a) to determine the temporal histopathological changes at the microelectrode brain tissue interface that coincide with recording failure; in addition 2) we will determine the changes in proinflammatory and neurotoxic factors at the implant site using retrieved probes and a new system that allows sampling of the institial fluid adjacent to the implant over time; and, finally c) we will test the hypothesis that agents that interfere with microglial activation and signaling are effective in attenuating neurodegeneration around the implanted silicon microelectrode arrays. The proposed research is likely to provide insight into the biological mechanisms that underlie chronic instability of silicon microelectrode arrays, and should lead to strategies to improve their usefulness for chronic applications.

描述（由申请人提供）：植入式硅微电极阵列技术是一种很有前途的方法，可用于基础研究和假体装置中的神经元活动的高密度、高分辨率采样。当前技术的主要局限之一是在长期应用中性能不一致，这限制了临床开发。虽然脑组织对植入电极的反应被认为是电不稳定的主要原因，但导致记录失败的确切机制尚不清楚。因此，了解硅微电极阵列的慢性不稳定性的机制，将导致策略，以提高其对慢性基础科学研究和各种神经假体应用的有用性。我们观察到植入成年大鼠运动皮质的硅微电极阵列周围存在持续的艾德-1免疫反应性，并观察到植入硅微电极阵列周围组织中的神经纤维密度和细胞体显着减少。在微电极穿刺对照中未观察到持续性艾德-1上调和神经变性，表明慢性炎症和神经元丢失不是由电极植入的初始机械创伤引起的，而是与脑组织对植入电极的反应相关。我们发现，我们的观察具有神经炎症介导的神经毒性成分的疾病的生物学特征。因此，我们假设，长期植入硅微电极阵列导致持续的巨噬细胞激活的微电极接口导致过度生产的促炎细胞因子和神经毒性因子，导致损失的神经元细胞体和纤维紧邻记录表面。为了验证我们的假设，提出了定量方法：a）确定与记录失败一致的微电极脑组织界面处的时间组织病理学变化;此外，2）我们将使用取回的探针和允许随时间推移对植入物附近的体液进行采样的新系统来确定植入部位的促炎因子和神经毒性因子的变化;最后c）我们将检验干扰小胶质细胞活化和信号传导的试剂在减弱植入的硅微电极阵列周围的神经变性中有效的假设。拟议的研究可能会提供深入了解的生物机制，硅微电极阵列的慢性不稳定性的基础，并应导致战略，以提高其实用性的长期应用。