Transcriptional characterization of the glial response due to chronic neural implantation of flexible microprobes

Kevin Joseph; Matthias Kirsch; Midori Johnston; Christian Münkel; Thomas Stieglitz; Carola A Haas; Ulrich G Hofmann

doi:10.1016/j.biomaterials.2021.121230

Transcriptional characterization of the glial response due to chronic neural implantation of flexible microprobes

Biomaterials. 2021 Dec:279:121230. doi: 10.1016/j.biomaterials.2021.121230. Epub 2021 Oct 29.

Authors

Kevin Joseph¹, Matthias Kirsch², Midori Johnston³, Christian Münkel⁴, Thomas Stieglitz⁵, Carola A Haas⁶, Ulrich G Hofmann⁷

Affiliations

¹ 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. Electronic address: kevin.joseph@uniklinik-freiburg.de.
² BrainLinks-BrainTools, University of Freiburg, Germany; Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Faculty of Medicine, University of Freiburg, Germany; BrainLinks-BrainTools, University of Freiburg, Germany; Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center- University of Freiburg, Germany.
⁴ 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.
⁵ BrainLinks-BrainTools, University of Freiburg, Germany; Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Faculty of Engineering, University of Freiburg, Germany.
⁶ Faculty of Medicine, University of Freiburg, Germany; Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center- University of Freiburg, Germany.
⁷ 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.

PMID: 34736153
DOI: 10.1016/j.biomaterials.2021.121230

Abstract

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.

Keywords: Astrocytes; Implantation; Microglia; Neural probes; Transcriptome analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes
Electrodes, Implanted
Microglia*
Neuroglia*
Rats
Rats, Sprague-Dawley