In vivo spatiotemporal patterns of oligodendrocyte and myelin damage at the neural electrode interface

Keying Chen; Steven M Wellman; Yalikun Yaxiaer; James R Eles; Takashi Dy Kozai

doi:10.1016/j.biomaterials.2020.120526

In vivo spatiotemporal patterns of oligodendrocyte and myelin damage at the neural electrode interface

Biomaterials. 2021 Jan:268:120526. doi: 10.1016/j.biomaterials.2020.120526. Epub 2020 Nov 23.

Authors

Keying Chen¹, Steven M Wellman¹, Yalikun Yaxiaer², James R Eles¹, Takashi Dy Kozai³

Affiliations

¹ Department of Bioengineering, University of Pittsburgh, USA; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, USA.
² Eberly College of Science, Pennsylvania State University, University Park, USA.
³ Department of Bioengineering, University of Pittsburgh, USA; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, USA; Center for Neuroscience, University of Pittsburgh, USA; McGowan Institute of Regenerative Medicine, University of Pittsburgh, USA; NeuroTech Center, University of Pittsburgh Brain Institute, USA. Electronic address: tk.kozai@pitt.edu.

Abstract

Intracortical microelectrodes with the ability to detect intrinsic electrical signals and/or deliver electrical stimulation into local brain regions have been a powerful tool to understand brain circuitry and for therapeutic applications to neurological disorders. However, the chronic stability and sensitivity of these intracortical microelectrodes are challenged by overwhelming biological responses, including severe neuronal loss and thick glial encapsulation. Unlike microglia and astrocytes whose activity have been extensively examined, oligodendrocytes and their myelin processes remain poorly studied within the neural interface field. Oligodendrocytes have been widely recognized to modulate electrical signal conductance along axons through insulating myelin segments. Emerging evidence offers an alternative perspective on neuron-oligodendrocyte coupling where oligodendrocytes provide metabolic and neurotrophic support to neurons through cytoplasmic myelin channels and monocarboxylate transporters. This study uses in vivo multi-photon microscopy to gain insights into the dynamics of oligodendrocyte soma and myelin processes in response to chronic device implantation injury over 4 weeks. We observe that implantation induces acute oligodendrocyte injury including initial deformation and substantial myelinosome formation, an early sign of myelin injury. Over chronic implantation periods, myelin and oligodendrocyte soma suffer severe degeneration proximal to the interface. Interestingly, wound healing attempts such as oligodendrogenesis are initiated over time, however they are hampered by continued degeneration near the implant. Nevertheless, this detailed characterization of oligodendrocyte spatiotemporal dynamics during microelectrode-induced inflammation may provide insights for novel intervention targets to facilitate oligodendrogenesis, enhance the integration of neural-electrode interfaces, and improve long-term functional performance.

Keywords: Bio-integration; Biocompatibility; Brain-computer interface; Foreign body response; Neural interfaces; Neurotechnology.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Microelectrodes
Myelin Sheath*
Neuroglia
Neurons
Oligodendroglia*

Abstract

Publication types

MeSH terms

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