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Characterization of immune response and peripheral nerve regeneration of implanted regenerative multi-electrode interface post-subchronic amputation.

机译：亚慢性截肢后植入的再生多电极界面的免疫应答和周围神经再生的表征。

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摘要

Interfacing high degree-of-freedom robotic prosthetics directly to the peripheral nervous system aims at improving the quotidian life of amputees. Despite advancements in robotics that have lead to human-like upper limb prosthetics, long-term interfacing has not been accomplished, thus voiding them from clinical use. Interfacing electrodes in the central nervous system fail due to the foreign body reaction and glial scar formation at the site of implantation. Concrete mechanisms for the failure of long-term Interfacing at the peripheral nervous level remain unclear. A regenerative multi-electrode interface (REMI) which allows for action potential recording as early as 7 days and provides support to bridge transected nerve gaps has been recently tested. However, the REMI, similarly to other electrode arrays, suffers from decay in action potential signal acquisition after an extended period of time. Today, amputees would not be interfaced immediately after amputation; therefore, the effects of a subchronic amputation must be studied to evaluate the peripheral nerve reaction to interfacing, in this case, implantation of a REMI. A 30-day subchronic amputation condition was simulated by transecting the sciatic nerve, ligating the distal stump, and suturing the proximal stump to the biceps femoris muscle of twelve female adult Lewis rats. Floating multi-electrode arrays comprising 18 Pt/Ir electrodes, placed in collagen-filled Polyurethane tubes, were implanted after subchronic amputation in the animals by suturing the stumps of transected sciatic nerve to the tube. The REMI , along with the nerve regenerate, was explanted after 15, 30, and 60 days. Reactive macrophages, visualized by immunofluorescence of ED1 labeling, showed a significant reduction in size between 15 and 60 days post REMI implantation for acute and subchronic amputation conditions. The progressive decreasing pattern indicates that scar formation around the electrodes does not directly affect the action potential signal acquisition; regardless, it may still play a minor role in interfacing failure. Axonal regeneration and remyelination were examined by immunolabeling with NF200 and P0, respectively. Axonal regeneration and remyelination between subchronic and acute amputation conditions revealed comparable results 15 post-injury. The complete remyelination of the axons correlates with the maximum percentage of active channels; however, it does not account for the eventual signal decay. Blood nerve barrier integrity was evaluated to determine whether tight junction formation and/or distribution has an effect on ion diffusion in the extracellular matrix. Through the use of anti-Claudin-1 antibodies, a progressive distribution and organization of tight junctions around and through the axons was observed for acute and subchronic amputation conditions. Foreign body response, axonal regeneration, remyelination, and BNB formation results indicate that a subchronic amputation does not significantly affect the peripheral nerve regenerating properties when compared to the acute amputation conditions. Further, it is hypothesized that tight junction concentration and distribution throughout the peripheral nerve plays an important role in the eventual failure of peripheral nervous interfacing.
机译：直接将高自由度的机器人假肢与周围神经系统连接，旨在改善截肢者的日常生活。尽管机器人技术的进步已经导致了类似于人的上肢假肢的形成，但长期接口尚未实现，因此使它们无法用于临床。由于异物反应和植入部位的胶质疤痕形成，中枢神经系统中的接口电极失效。周围神经水平长期接口失败的具体机制仍不清楚。最近已经测试了一种再生多电极接口（REMI），该接口可在7天之内记录动作电位并为桥接横切的神经间隙提供支持。然而，与其他电极阵列类似，REMI在延长的时间段后遭受动作电位信号采集的衰减。今天，截肢后不会立即与截肢者交往；因此，必须研究亚慢性截肢的效果，以评估周围神经对接口（在这种情况下为REMI植入）的反应。通过切断坐骨神经，结扎远端残端并将近端残端缝合到十二只成年雌性Lewis大鼠股二头肌上，模拟了30天的亚慢性截肢情况。在亚慢性截肢后，通过将横切坐骨神经的残端缝合到管子中，将包含18个Pt / Ir电极的浮动多电极阵列放置在胶原蛋白填充的聚氨酯管中。在15、30和60天后，将REMI与神经再生一起植入。通过对ED1标记进行免疫荧光观察，可观察到反应性巨噬细胞在急性和亚慢性截肢情况下REMI植入后15至60天之间大小显着减小。逐渐减小的模式表明电极周围的疤痕形成不会直接影响动作电位信号的获取；无论如何，它在接口故障中仍可能只扮演次要角色。通过分别用NF200和P0进行免疫标记来检查轴突再生和髓鞘再生。亚慢性和急性截肢条件之间的轴突再生和髓鞘再生显示出可比的损伤后结果15。轴突的完全髓鞘再生与活动通道的最大百分比有关。但是，这并不能说明最终的信号衰减。评估血液神经屏障的完整性以确定紧密连接的形成和/或分布是否对细胞外基质中的离子扩散产生影响。通过使用抗Claudin-1抗体，观察到急性和亚慢性截肢情况下轴突周围和穿过轴突的紧密连接的逐步分布和组织。异物反应，轴突再生，髓鞘再生和BNB形成结果表明，与急性截肢情况相比，亚慢性截肢术不会显着影响周围神经的再生特性。此外，假设在整个周围神经中紧密的连接浓度和分布在最终的周围神经接口失败中起重要作用。

著录项

  • 作者

    Sanchez Useche, Camilo Andres.;

  • 作者单位

    The University of Texas at Arlington.;

  • 授予单位 The University of Texas at Arlington.;
  • 学科 Biomedical engineering.;Biology.;Neurosciences.
  • 学位 M.S.
  • 年度 2012
  • 页码 90 p.
  • 总页数 90
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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