Spatiotemporal patterns of gene expression around implanted silicon electrode arrays.

Spatiotemporal patterns of gene expression around implanted silicon electrode arrays.
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植入硅电极阵列周围基因表达的时空模式。

DOI:
10.1088/1741-2552/abf2e6
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发表时间:
2021-04-27
影响因子:
4
通讯作者:
Purcell EK
Purcell EK
中科院分区:
工程技术2区
文献类型:
--
作者:
Thompson CH;Saxena A;Heelan N;Salatino J;Purcell EK

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大脑皮质内接口是一种不断发展的技术,在临床和研究应用中的潜力越来越大。对这些设备的慢性组织反应传统上以胶质瘢痕形成、炎症、氧化应激、神经元丢失和血脑屏障破坏为特征。组织对植入设备的反应的全部复杂性仍在调查中。在这项研究中,我们利用核糖核酸测序技术来鉴定植入硅微电极阵列周围的界面(100μm内)和远端(距植入体500μm)脑组织中的时空基因表达模式。天真的、未植入的组织作为对照。这些数据在界面组织与幼稚组织(157个DE基因)、界面组织与远端组织(94个DE基因)和远端组织与幼稚组织(21个DE基因)的对比中显示出显著的总体差异表达(DE)。我们的结果捕捉到了先前描述的异物反应的机制,如星形胶质包被,以及尚未在留置神经技术的背景下描述的新机制。特别是,我们观察到了多个神经元相关基因的扰动,这些基因可能会影响设备界面上神经元的内在功能和结构。除了神经元相关基因,这项研究的结果还发现了与参与慢性组织反应的少突胶质细胞、小胶质细胞和星形胶质细胞相关的基因中显著的DE。这项研究的结果增加了对大脑组织反应复杂性的基本了解,并为未来研究植入电子与中枢神经系统组织的生物整合提供了一个扩展的工具包。
Intracortical brain interfaces are an ever evolving technology with growing potential for clinical and research applications. The chronic tissue response to these devices traditionally has been characterized by glial scarring, inflammation, oxidative stress, neuronal loss, and blood-brain barrier disruptions. The full complexity of the tissue response to implanted devices is still under investigation. In this study, we have utilized RNA-sequencing to identify the spatiotemporal gene expression patterns in interfacial (within 100μm) and distal (500μm from implant) brain tissue around implanted silicon microelectrode arrays. Naïve, unimplanted tissue served as a control. The data revealed significant overall differential expression (DE) in contrasts comparing interfacial tissue vs naïve (157 DE genes), interfacial vs. distal (94 DE genes), and distal vs. naïve tissues (21 DE genes). Our results captured previously characterized mechanisms of the foreign body response, such as astroglial encapsulation, as well as novel mechanisms which have not yet been characterized in the context of indwelling neurotechnologies. In particular, we have observed perturbations in multiple neuron-associated genes which potentially impact the intrinsic function and structure of neurons at the device interface. In addition to neuron-associated genes, the results presented in this study identified significant DE in genes which are associated with oligodendrocyte, microglia, and astrocyte involvement in the chronic tissue response. The results of this study increase the fundamental understanding of the complexity of tissue response in the brain and provide an expanded toolkit for future investigation into the bio-integration of implanted electronics with tissues in the central nervous system.
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