Neuroelectronic Systems, Department of Neurosurgery, Medical Center, University of Freiburg, Germany; Department of Neurosurgery, Medical Center University of Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany; BrainLinks-BrainTools, University of Freiburg, Germany.
BrainLinks-BrainTools, University of Freiburg, Germany; Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Biomaterials. 2021 Dec;279:121230. doi: 10.1016/j.biomaterials.2021.121230. Epub 2021 Oct 29.
Long term implantation of (micro-)probes into neural tissue causes unique and disruptive responses. In this study, we investigate the transcriptional trajectory of glial cells responding to chronic implantation of 380 μm flexible micro-probes for up to 18 weeks. Transcriptomic analysis shows a rapid activation of microglial cells and a strong reactive astrocytic polarization, both of which are lost over the chronic of the implant duration. Animals that were implanted for 18 weeks show a transcriptional profile similar to non-implanted controls, with increased expression of genes associated with wound healing and angiogenesis, which raises hope of a normalization of the neuropil to the pre-injury state when using flexible probes. Nevertheless, our data shows that a subset of genes upregulated after 18 weeks belong to the family of immediate early genes, which indicates that structural and functional remodeling is not complete at this time point. Our results confirm and extend previous work on the molecular changes resulting from the presence of neural probes and provide a rational basis for developing interventional strategies to control them.
长期将（微）探针植入神经组织会引起独特且具有破坏性的反应。在这项研究中，我们研究了对长达 18 周的慢性植入 380μm 柔性微探针的神经胶质细胞的转录轨迹。转录组分析显示小胶质细胞迅速激活和强烈的反应性星形胶质细胞极化，这两者在植入持续时间的慢性期都会消失。植入 18 周的动物表现出与未植入对照相似的转录谱，与创伤愈合和血管生成相关的基因表达增加，这为使用柔性探针使神经毡恢复到损伤前状态带来了希望。然而，我们的数据表明，18 周后上调的一组基因属于即时早期基因家族，这表明此时结构和功能重塑尚未完成。我们的结果证实并扩展了先前关于神经探针存在引起的分子变化的工作，并为开发控制这些变化的干预策略提供了合理的依据。
