Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
J Neural Eng. 2012 Aug;9(4):046020. doi: 10.1088/1741-2560/9/4/046020. Epub 2012 Jul 25.
An estimated 25 million people in the US alone rely on implanted medical devices, ∼2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ∼50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.
据估计，仅美国就有 2500 万人依赖植入式医疗设备，其中约 250 万人植入神经系统。尽管许多设备多年来性能良好，但宿主对医疗设备的反应通常严重限制了组织整合和长期性能。这种宿主反应在皮层内微电极中被认为是特别受限的，在这种情况下，已经表明神经胶质细胞包封和局部神经元细胞丢失伴随着皮层内微电极的植入。由于神经元集合必须在电极的约 50 µm 范围内才能获得神经元尖峰和局部场电位，因此，深入了解设备-组织界面的分子和细胞环境一直是大量研究的主题。不幸的是，与设备功能相关的疤痕成熟的免疫组织化学研究尚无定论。因此，在这里，我们在慢性存活模型中呈现了皮层内微电极植入和皮层刺伤后细胞事件和血脑屏障（BBB）稳定性的详细定量研究。与刺伤动物相比，我们在植入设备的组织中发现了神经元存活的两种明显相反的多相分布模式。对于慢性植入动物，我们观察到血液衍生/创伤诱导和中枢神经系统衍生的炎症标志物之间的双相范例，在界面处驱动神经退行性变。相比之下，刺伤动物表现出中枢神经系统介导的神经退行性环境。这些数据共同为慢性神经炎症事件对 BBB 破坏和局部神经退行性变的多种作用的可能性提供了有价值的见解，同时也表明在设计稳定神经界面的治疗策略时考虑多相神经炎症动力学的重要性。
