Short-Term Effects of Gamma Stimulation on Neuroinflammation at the Tissue-Electrode Interface in Motor Cortex

Emily Boltcreed; Alpaslan Ersöz; Martin Han; George C McConnell

doi:10.1016/j.neurom.2023.11.003

Short-Term Effects of Gamma Stimulation on Neuroinflammation at the Tissue-Electrode Interface in Motor Cortex

Neuromodulation. 2024 Apr;27(3):500-508. doi: 10.1016/j.neurom.2023.11.003. Epub 2023 Dec 13.

Authors

Emily Boltcreed¹, Alpaslan Ersöz², Martin Han³, George C McConnell⁴

Affiliations

¹ Stevens Institute of Technology, Hoboken, NJ; Semcer Center for Healthcare Innovation, Hoboken, NJ.
² Mechanical Engineering Department, Carnegie Mellon University, Pittsburgh, PA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT.
³ Department of Biomedical Engineering, University of Connecticut, Storrs, CT.
⁴ Stevens Institute of Technology, Hoboken, NJ; Semcer Center for Healthcare Innovation, Hoboken, NJ. Electronic address: gmcconne@stevens.edu.

PMID: 38099883
PMCID: PMC10990794 (available on 2025-04-01)
DOI: 10.1016/j.neurom.2023.11.003

Abstract

Objectives: The reliability of long-term neural recordings as therapeutic interventions for motor and sensory disorders is hampered by the brain tissue response. Previous work showed that flickering light at gamma frequencies (ie, 20-50 Hz) causes enhanced microglial recruitment in the visual cortex. The effects of gamma stimulation on glial cells surrounding implanted neural electrodes are not well understood. We hypothesized that invasive stimulation in the gamma frequency band increases microglial recruitment in the short term and reduces astrogliosis at the tissue-electrode interface.

Materials and methods: Male Long Evans rats were implanted with dual-shank silicon microelectrode arrays into the motor cortex. After implantation, rats received one hour of 40-Hz stimulation at a constant current of 10 μA using charge-balanced, biphasic pulses on one shank, and the other shank served as the nonstimulated control. Postmortem, tissue sections were stained with ectodermal dysplasia 1 (ED1) for activated microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and 4',6-diamidino-2-phenylindole (DAPI) for nonspecific nuclei. Fluorescent intensity and cell number as a function of distance from the tissue-electrode interface were used to quantify all stained sections.

Results: Fluorescent intensity for ED1 was nearly 40% lower for control than for stimulated sites (0-500 μm away from the implant), indicating increased microglial recruitment to the stimulated site (p < 0.05). Fluorescent intensity for GFAP was >67% higher for control than for stimulated sites (0-500 μm away from the implant), indicating reduced astrogliosis at the stimulated site (p < 0.05). No differences were observed in DAPI-stained sections between conditions.

Conclusions: These results suggest that short-term gamma stimulation modulates glial recruitment in the immediate vicinity of the microelectrode. Future studies will investigate the long-term effects of gamma stimulation on glial recruitment at the tissue-electrode interface as a strategy to improve long-term recording reliability.

Keywords: Brain-machine interface; gamma stimulation; glial response; motor cortex; neuroinflammation.

MeSH terms

Animals
Electrodes, Implanted
Gliosis
Male
Microelectrodes
Motor Cortex*
Neuroinflammatory Diseases*
Rats
Rats, Long-Evans
Reproducibility of Results

Grants and funding

R01 DC014044/DC/NIDCD NIH HHS/United States