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神经电极植入引起 NG2 胶质细胞活性的体内时空动力学。

In vivo spatiotemporal dynamics of NG2 glia activity caused by neural electrode implantation.

机构信息

Department of Bioengineering, University of Pittsburgh, United States; Center for the Basis of Neural Cognition, United States.

Department of Bioengineering, University of Pittsburgh, United States; Center for the Basis of Neural Cognition, United States; Center for Neuroscience, University of Pittsburgh, United States; McGowan Institute of Regenerative Medicine, University of Pittsburgh, United States; NeuroTech Center, University of Pittsburgh Brain Institute, United States.

出版信息

Biomaterials. 2018 May;164:121-133. doi: 10.1016/j.biomaterials.2018.02.037. Epub 2018 Feb 20.

Abstract

Neural interface technology provides direct sampling and analysis of electrical and chemical events in the brain in order to better understand neuronal function and treat neurodegenerative disease. However, intracortical electrodes experience inflammatory reactions that reduce long-term stability and functionality and are understood to be facilitated by activated microglia and astrocytes. Emerging studies have identified another cell type that participates in the formation of a high-impedance glial scar following brain injury; the oligodendrocyte precursor cell (OPC). These cells maintain functional synapses with neurons and are a crucial source of neurotrophic support. Following injury, OPCs migrate toward areas of tissue injury over the course of days, similar to activated microglia. The delayed time course implicates these OPCs as key components in the formation of the outer layers of the glial scar around the implant. In vivo two-photon laser scanning microscopy (TPLSM) was employed to observe fluorescently-labeled OPC and microglia reactivity up to 72 h following probe insertion. OPCs initiated extension of cellular processes (2.5 ± 0.4 μm h) and cell body migration (1.6 ± 0.3 μm h) toward the probe beginning 12 h after insertion. By 72 h, OPCs became activated at a radius of about 190.3 μm away from the probe surface. This study characterized the early spatiotemporal dynamics of OPCs involved in the inflammatory response induced by microelectrode insertion. OPCs are key mediators of tissue health and are understood to have multiple fate potentials. Detailed spatiotemporal characterization of glial behavior under pathological conditions may allow identification of alternative intervention targets for mitigating the formation of a glial scar and subsequent neurodegeneration that debilitates chronic neural interfaces.

摘要

神经接口技术提供了对大脑中电和化学事件的直接采样和分析,以便更好地了解神经元功能并治疗神经退行性疾病。然而,脑内电极会经历炎症反应,从而降低长期稳定性和功能,而被激活的小胶质细胞和星形胶质细胞被认为是炎症反应的促进因素。新兴研究已经确定了另一种参与脑损伤后形成高阻抗神经胶质瘢痕的细胞类型;少突胶质前体细胞 (OPC)。这些细胞与神经元保持功能性突触连接,是神经营养支持的重要来源。损伤后,OPC 会在数天内向组织损伤区域迁移,类似于被激活的小胶质细胞。延迟的时间过程表明这些 OPC 是植入物周围神经胶质瘢痕外层形成的关键组成部分。在体内,使用双光子激光扫描显微镜 (TPLSM) 观察到荧光标记的 OPC 和小胶质细胞反应,直到探针插入后 72 小时。OPC 开始延伸细胞过程(2.5±0.4μm/h)和细胞体迁移(1.6±0.3μm/h),向探针插入后 12 小时开始向探针迁移。到 72 小时时,OPC 在距探针表面约 190.3μm 的半径处被激活。本研究描述了 OPC 参与微电极插入诱导的炎症反应的早期时空动力学。OPC 是组织健康的关键介质,并且具有多种命运潜力。对病理条件下神经胶质行为的详细时空特征进行描述,可能有助于确定减轻神经胶质瘢痕形成和随后的神经退行性变的替代干预靶点,从而削弱慢性神经接口。

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