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Spatial Transcriptomics as a Novel Approach to Redefine Electrical Stimulation Safety.

Quentin A Whitsitt1, Beomseo Koo2, Mahmut Emin Celik3

  • 1Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United States.

Frontiers in Neuroscience
|August 5, 2022
PubMed
Summary

Spatial transcriptomics reveals gene expression changes in the brain following electrical stimulation, offering new insights beyond traditional safety limits. This advanced technique helps refine safety standards for central nervous system stimulation by analyzing biological responses at a molecular level.

Keywords:
carbon fiber microelectrode (CFME)in vivo stimulationmicrostimulationsafetyspatial transcriptomics

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Bioengineering

Background:

  • Current electrical stimulation safety standards for the central nervous system rely on historical histological damage assessments.
  • The "Shannon limits" provide basic calculations for safe stimulation intensity based on charge per phase and charge density.
  • Advances in molecular biology necessitate more detailed investigations into the physiological effects of neural stimulation.

Purpose of the Study:

  • To explore the biological response to electrical stimulation in the rat visual cortex using spatial transcriptomics (ST).
  • To compare the effects of different electrode types and stimulation parameters on gene expression.
  • To integrate ST with histological analysis for a comprehensive assessment of stimulation-induced tissue changes.

Main Methods:

  • Electrical stimulation was applied to the rat visual cortex using acute and chronic implantation of carbon fiber ultramicroelectrodes and microwire electrodes.
  • Stimulation parameters (charge and charge density) were varied above and below established tissue damage thresholds.
  • Spatial transcriptomics (Visium platform) was performed, allowing simultaneous immunohistochemistry and gene expression analysis within tissue samples.

Main Results:

  • Unique spatial patterns of gene expression related to inflammation, cell cycle progression, and neuronal plasticity were identified.
  • Acute stimulation showed increased inflammatory and plasticity-related genes around the stimulating electrode.
  • Chronic stimulation revealed increased inflammatory and cell cycle genes with microwire electrodes compared to controls and carbon fiber electrodes.

Conclusions:

  • Spatial transcriptomics provides a novel method to assess biological responses to electrical brain stimulation.
  • The findings offer a deeper understanding of cellular processes affected by stimulation beyond traditional damage metrics.
  • This approach can generate new hypotheses and inform the development of improved safety standards for neural stimulation therapies.