Prolonged Targeted Cardiovascular Epidural Stimulation Improves Immunological Molecular Profile: A Case Report in Chronic Severe Spinal Cord Injury

Figure 1. Site of implantation of the electrode array and stimulating configuration for cardiovascular stability-spinal cord epidural stimulation (CV-scES). (A) Sagittal and Axial MRI sections of the lumbosacral cord were used to calculate the cross-sectional area of the spinal cord and cerebrospinal fluid to create a 3-D reconstruction of the spinal cord at the lumbosacral enlargement. (B) Sagittal x-rays indicating the final placement of the electrode array. (C) 3-D reconstruction of the electrode array relative to the lumbosacral enlargement. (D) Graphical representation of electrode configuration for CV-scES, configuration uses two programs (P1 and P2) running concurrently. Cathodes are represented in black and anodes in gray. Each program runs with an independent stimulating amplitude, pulse width, and frequency.

Figure 2. Mean arterial pressure (MAP) and cerebral blood flow during the orthostatic challenge are improved with CV-scES. (A) Cerebral mean arterial pressure (cMAP), (B) mean cerebral blood flow (mCBFv) during the head-up tilt maneuver, and (C) relationship between cMAP and mCBFv pre CV-scES (black circles) and post CV-scES (gray squares). Note that the participant was only able to tolerate 10-min in the 70° head-up tilt position pre-CV-scES, but was able to tolerate 30-min post-CV-scES.

Figure 3. Whole blood gene expression is profoundly changed in an individual with spinal cord injury (SCI) compared with able-bodied (AB) individuals. (A) Principal component analysis (PCA) shows patterns of gene expression. Black symbols represent data obtained from three AB individuals, each sampled once. Red symbols represent data obtained from the individual with chronic SCI, pre and post CVscES intervention. PCA gene expression in the individual with SCI is similar pre- and post-intervention along the Y-axis (PC2) and X-axis (PC1), but is different on the Z-axis (PC3) axis. (B) The number of differentially expressed genes (up- or down-regulated) is shown. (C) Downregulated genes: multiple bioinformatics platforms independently identified pathways enriched following usual care in the participant with SCI, which are related to adaptive immunity. (D) Two cell type bioinformatics platforms identified natural killer (NK) cell genes enriched among downregulated genes. (E) Upregulated genes: multiple bioinformatics platforms independently identified pathways enriched following usual care in the participant with SCI that are related to viral and eukaryotic transcription and translation. (F)…

Figure 4. Whole blood gene expression is profoundly changed within an individual with SCI after 80 sessions of CV scES. (A) The volcano plot shows several differentially expressed genes within the participant following 97-sessions of CV-scES. Downregulated genes (green) include pro-inflammatory genes of interest, such as JAK2, RHOA, and toll-like receptors (TLRs). Upregulated genes (red) include genes of interest related to adaptive immunity, e.g., CD44 and HLA related molecules (MHCI and MHCII). (B) The numbers of differentially expressed genes are shown. (C) Downregulated genes: multiple bioinformatics platforms independently identified pathways related to pro-inflammatory TLR signaling. (D) Cell type bioinformatics platforms identified whole blood and dendritic cells enriched among downregulated genes. (E) Upregulated genes: multiple bioinformatics platforms independently identified pathways related to adaptive immunity. (F) Two cell type bioinformatics platforms identified peripheral blood and CD14+ monocytes enriched among upregulated genes.