FIGURE 5.

Quantitative immunohistochemistry of chronically implanted samples indicates that both device type and stimulation delivery may influence traditional safety metrics (neuronal density, glial reactivity). (A) Tissue collected at the 4-week time point from a sample implanted with a MWA that delivered no stimulation shows relatively minimal local glial (GFAP) reactivity or neuronal loss (NeuN density). (B) Tissue collected from a sample implanted with a MWA that delivered electrical stimulation following 4 weeks of device implantation shows evidence of local gliosis and neuronal loss. (C) Tissue collected from a sample implanted with a HDCF that delivered electrical stimulation following 4 weeks of device implantation shows lesser evidence of local gliosis and neuronal loss in comparison to the MWA/Stimulation sample shown in panel (B). (D) Spatial expression of Gfap counts at increasing distances from the electrode tract in all three chronic samples align with IHC results. (E) Spatial expression of the gene Rbfox3, which encodes the NeuN protein, at increasing distances from the electrode tract in all three chronic samples. An advantage of the spatial transcriptomics assay is that spatial profiles of gene expression can be compared directly with more traditional quantitative immunohistochemistry metrics. Asterisks denote estimated implant site and arrows denote orientation (L: lateral, A: anterior). Scale bars: 1.0 mm.