Kolarcik Christi L, Castro Carlos A, Lesniak Andrew, Demetris Anthony J, Fisher Lee E, Gaunt Robert A, Weber Douglas J, Cui X Tracy
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States of America. Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegic Mellon University, Pittsburgh, PA, United States of America. McGowan Institute for Regenerative Medicine, Pittsburgh, PA, United States of America. Systems Neuroscience Center, Pittsburgh, PA, United States of America. Live Like Lou Center for ALS Research, Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, United States of America.
J Neural Eng. 2020 Jul 10;17(4):046012. doi: 10.1088/1741-2552/ab94d7.
Neural interfacing technologies could significantly improve quality of life for people living with the loss of a limb. Both motor commands and sensory feedback must be considered; these complementary systems are segregated from one another in the spinal nerve.
The dorsal root ganglion-ventral root (DRG-VR) complex was targeted chronically with floating microelectrode arrays designed to record from motor neuron axons in the VR or stimulate sensory neurons in the DRG. Hematoxylin and eosin and Nissl/Luxol fast blue staining were performed. Characterization of the tissue response in regions of interest and pixel-based image analyses were used to quantify MAC387 (monocytes/macrophages), NF200 (axons), S100 (Schwann cells), vimentin (fibroblasts, endothelial cells, astrocytes), and GLUT1 (glucose transport proteins) reactivity. Implanted roots were compared to non-implanted roots and differences between the VR and DRG examined.
The tissue response associated with chronic array implantation in this peripheral location is similar to that observed in central nervous system locations. Markers of inflammation were increased in implanted roots relative to control roots with MAC387 positive cells distributed throughout the region corresponding to the device footprint. Significant decreases in neuronal density and myelination were observed in both the VR, which contains only neuronal axons, and the DRG, which contains both neuronal axons and cell bodies. Notably, decreases in NF200 in the VR were observed only at implant times less than ten weeks. Observations related to the blood-nerve barrier and tissue integrity suggest that tissue remodeling occurs, particularly in the VR.
This study was designed to assess the viability of the DRG-VR complex as a site for neural interfacing applications and suggests that continued efforts to mitigate the tissue response will be critical to achieve the overall goal of a long-term, reliable neural interface.
神经接口技术可显著改善肢体缺失者的生活质量。必须同时考虑运动指令和感觉反馈;这两个互补系统在脊神经中是相互分离的。
采用漂浮微电极阵列长期靶向背根神经节 - 腹根(DRG - VR)复合体,该阵列旨在记录腹根中运动神经元轴突的信号或刺激背根神经节中的感觉神经元。进行苏木精和伊红染色以及尼氏/卢戈氏快蓝染色。利用感兴趣区域的组织反应特征和基于像素的图像分析来量化MAC387(单核细胞/巨噬细胞)、NF200(轴突)、S100(施万细胞)、波形蛋白(成纤维细胞、内皮细胞、星形胶质细胞)和GLUT1(葡萄糖转运蛋白)的反应性。将植入的神经根与未植入的神经根进行比较,并检查腹根和背根神经节之间的差异。
在这个外周位置进行慢性阵列植入所引发的组织反应与在中枢神经系统位置观察到的相似。与对照根相比,植入根中的炎症标志物增加,MAC387阳性细胞分布在与设备覆盖区域相对应的整个区域。在仅包含神经元轴突的腹根和既包含神经元轴突又包含细胞体的背根神经节中,均观察到神经元密度和髓鞘形成显著降低。值得注意的是,仅在植入时间少于十周时,腹根中的NF200才出现降低。与血 - 神经屏障和组织完整性相关的观察结果表明发生了组织重塑,尤其是在腹根中。
本研究旨在评估DRG - VR复合体作为神经接口应用部位的可行性,并表明持续努力减轻组织反应对于实现长期、可靠神经接口的总体目标至关重要。