Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model

Figures

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  FIGURE 1. Experimental schedule and the efferent vagus nerve stimulation strategy (eVNS). (a) Experimental schedule outlining the rat model and eVNS testing. (b) Schematic drawing of the abdominal vagus nerve cuff electrode array. The middle electrode pair (E3‐E4) provided blocking stimulation (26 kHz) and the distal electrode pair (E5‐E6) delivered an activation stimulation (15 Hz). The proximal electrode pair (E1‐E2) were used to record evoked compound action potentials (ECAPs). (c) Illustrative ECAP recordings from an acutely implanted, metabolically challenged rat (not used in this study) during no block (224 µA threshold) and during 26 kHz blocking

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  FIGURE 2. Dose effects of acute eVNS during an oral glucose tolerance test. (a) Representative example shows a reduction (indicated by blue shading) in glycemia during 2 dB eVNS (1 h, blue line) compared to control (no stimulation, dotted black line). (b) Changes in the area under the curve (AUC) of glycemia during acute eVNS compared to internal unstimulated control. (c) Changes in glycemia AUC when different current levels above ECAP threshold were applied. Data were compared to the control glycemic response within the same animal and show the difference in glycemia from baseline (T = 0). Data in (b,c) show mean ± SEM, symbols are individual subject values, and significance was accepted as values p < 0.05 (indicated by “*”)

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  FIGURE 3. Chronic stability of eVNS during an oral glucose tolerance test following chronic implantation. (a) Average net changes in glucose (n = 6), compared to baseline, during 60 min of 2 dB eVNS and no stimulation (control). (b) Comparison of the glycemic AUC during 1 h of eVNS and no stimulation (control). (c) Comparison of the insulin AUC during eVNS and no stimulation (control). (d) Comparison of the glucagon AUC during eVNS and no stimulation (control). Data in (b–d) show AUC of the change from baseline (T = 0). Graphs show mean ± SEM, symbols represent individual subject values, and significance was accepted as values p < 0.05 (indicated by ‘*’)

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  FIGURE 4. Histological assessment of the vagus nerve following chronic stimulation and implantation. Hematoxylin and eosin staining was used to assess histopathology in neural tissue proximal (a) to the implant, at E1‐E2 (b), E3‐E4 (c), and E5‐E6 (d). (e) The cross‐sectional area of anterior vagus nerve fascicles was analyzed proximal to the implantation site and in tissue adjacent to electrode pairs. Scale bar for (a–d) represents 100 µm and data show mean ± SEM, with significance accepted as values p < 0.05