Continuous vs. intermittent chronic vagus nerve stimulation: effects on T-cell dependent antibody response, heart rate variability and body weight in immunized mice

Figures

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  Fig. 1. Mice were subjected to either no stimulation or to one of two chronic VNS schedules, for 4 weeks; effective stimulation was verified by measuring induced heart rate drop daily and adjusting stimulation amplitude accordingly. A VNS stimulation was administered daily to three groups of mice: no stimulation, continuous burst VNS, and twice daily VNS. B Average heart rate drop and stimulus intensity over the 4-week treatment period from one representative animal in the Twice Daily group. Heart rate drop represents an average of heart rate responses to 2 VNS trains per day. C Same as B, but from the Continuous Burst group. Heart rate drop represents average response to 144 VNS trains per day. D HRV separated into LF and HF components for each treatment group from 1 day before start of VNS to 3 days before end of treatment period. E HF power of HRV and (F) LF power of HRV, averaged over the first week of VNS treatment compared between groups

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  Fig. 2. Continuous burst stimulation reduces antibody production against NP-CGG. A, B Antibody titers at day 0, 7, and 14 for NP2 IgG, (C, D) NP25 IgG, (D, E) Total IgG, (F) NP25 IgM, (G) Total IgM for No Stimulation, Twice Daily and Continuous Burst animals. Linear regression of antibody titers is plotted per group and slope and y-intercept is shown in the tables below. Bar plots are shown for NP2 IgG, NP25 IgG and Total IgG to allow for visual comparison of effect size, but are not used for statistical comparison

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  Fig. 3. Continuous burst stimulation reduces body weight, spleen size and cellularity, compared to Twice Daily stimulation and No Stimulation. A Body weight, in grams, of No Stimulation (top), Twice Daily (middle), and Continuous Burst-stimulated animals (bottom). Comparison of (B) spleen weight, (C) total spleen cells, (D) total non-lymphocyte splenocytes, (E) total B cells, (F) total GCB cells, and (G) NP + GCB cells, (H) total CD4 + T cells, (I) total CD8 + T cells between stimulation groups. J Comparison of non-lymphocyte splenocytes normalized to total splenocytes. K Same as (J) but for B cells, (L) CD4 + T Cells, (M) CD8 + T cells. N Examples of stained spleen sections (top) and segmented ROIs (bottom) used to compare (O) red pulp cell area, (P) B cell area, and (Q) T cell area between stimulation groups