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神经植入物与实质组织界面的超微结构分析揭示了显著的神经再生以及限制植入物电生理功能的屏障。

Ultrastructural Analysis of Neuroimplant-Parenchyma Interfaces Uncover Remarkable Neuroregeneration Along-With Barriers That Limit the Implant Electrophysiological Functions.

作者信息

Sharon Aviv, Shmoel Nava, Erez Hadas, Jankowski Maciej M, Friedmann Yael, Spira Micha E

机构信息

Department of Neurobiology, The Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem, Israel.

The Charles E. Smith Family and Prof. Joel Elkes Laboratory for Collaborative Research in Psychobiology, The Hebrew University of Jerusalem, Jerusalem, Israel.

出版信息

Front Neurosci. 2021 Nov 22;15:764448. doi: 10.3389/fnins.2021.764448. eCollection 2021.

Abstract

Despite increasing use of multielectrode array (MEA) implants for basic research and medical applications, the critical structural interfaces formed between the implants and the brain parenchyma, remain elusive. Prevailing view assumes that formation of multicellular inflammatory encapsulating-scar around the implants [the foreign body response (FBR)] degrades the implant electrophysiological functions. Using gold mushroom shaped microelectrodes (gMμEs) based perforated polyimide MEA platforms (PPMPs) that in contrast to standard probes can be thin sectioned along with the interfacing parenchyma; we examined here for the first time the interfaces formed between brains parenchyma and implanted 3D vertical microelectrode platforms at the ultrastructural level. Our study demonstrates remarkable regenerative processes including neuritogenesis, axon myelination, synapse formation and capillaries regrowth in contact and around the implant. In parallel, we document that individual microglia adhere tightly and engulf the gMμEs. Modeling of the formed microglia-electrode junctions suggest that this configuration suffice to account for the low and deteriorating recording qualities of MEA implants. These observations help define the anticipated hurdles to adapting the advantageous 3D vertical-electrode technologies to settings, and suggest that improving the recording qualities and durability of planar or 3D electrode implants will require developing approaches to eliminate the insulating microglia junctions.

摘要

尽管多电极阵列(MEA)植入物在基础研究和医学应用中的使用日益增加,但植入物与脑实质之间形成的关键结构界面仍不清楚。普遍观点认为,植入物周围形成的多细胞炎性包裹性瘢痕[异物反应(FBR)]会降低植入物的电生理功能。使用基于金蘑菇形微电极(gMμEs)的穿孔聚酰亚胺MEA平台(PPMPs),与标准探针不同,该平台可以与界面实质一起进行薄切片;我们首次在超微结构水平上研究了脑实质与植入的3D垂直微电极平台之间形成的界面。我们的研究证明了显著的再生过程,包括神经突发生、轴突髓鞘形成、突触形成以及植入物周围和与之接触处的毛细血管再生。同时,我们记录到单个小胶质细胞紧密粘附并吞噬gMμEs。对形成的小胶质细胞-电极连接的建模表明,这种结构足以解释MEA植入物记录质量低且不断恶化的原因。这些观察结果有助于确定将有利的3D垂直电极技术应用于实际情况时预期会遇到的障碍,并表明提高平面或3D电极植入物的记录质量和耐用性将需要开发消除绝缘性小胶质细胞连接的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8645653/d6319df85424/fnins-15-764448-g001.jpg

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