Fig. 4: Sacral splanchnic nerve modulation for colitis treatment.
From: Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation

a Schematic and microscopic image of the NeuroRing implant that wrapped around the sacral splanchnic nerve. EEG signals were recorded while ultrasound-induced electrical stimulation of the sacral nerves was performed. b EEG (top) recorded over parietal cortex and comparison of the power spectrum (middle) and its derived quantified power spectral density (bottom) for sham control, US alone, and NeuroRing showing the significant enhancement in rats treated with ultrasound-induced electrical stimulation. Sham control refers to the sham operation and normal drinking water group. US alone refers to the sham operation and drinking DSS group. Bottom: the black dashed box intuitively reflects the significant enhancement of ultrasound-induced electrical stimulation, especially in the range of 50–80 Hz. c Expression levels of NE (sympathetic endocrine hormones) and PP (vagal endocrine hormones) in blood samples. d Schematic representation of the protective mechanism of US-triggered NeuroRing in DSS-induced colitis. Neuromodulation alleviates DSS-induced colitis by inhibiting macrophage M1 polarization and promoting M2 polarization. e Immunostaining for M1 macrophages represented by CD11b (red) and CD11c (green) of colon tissue. Bottom: the quantification (bottom) of CD11b and CD11c. CD11b: PUS/Neuro = 1.5801E-15; PUS/Sham = 6.2921E-16; PNeuro/Sham = 0.052. CD11c: PUS/Neuro = 7.7803E-18; PUS/Sham = 1.9047E-18; PNeuro/Sham = 0.049. f Immunostaining for M2 macrophages represented by CD206 (red) and F4/80 (green). Bottom: the quantification (bottom) of CD206 and F4/80. CD206: PUS/Neuro = 3.2E-12; PUS/Sham = 1.6497E-10; PNeuro/Sham = 0.009536. F4/80: PUS/Neuro = 4.4252E-18; PUS/Sham = 4.4554E-18; PNeuro/Sham = 0.962116. g Immunostaining for HO-1 (red) and Caspase1 (green). Bottom: quantification (bottom) of HO-1 and Caspase1. HO-1: PUS/Neuro = 9.3436E-20; PNeuro/Sham = 1.3455E-19. Caspase1: PUS/Neuro = 5.8124E-10; PUS/Sham = 1.7891E-10; PNeuro/Sham = 0.083595. h–j IL-2 (h), IL-10 (i) immunofluorescent stain, and H&E stain (j) images of colon tissue. k–m Relative expression level measured from (k) IL-2 and (l) IL-10 immunofluorescent staining and (m) H&E stain images. IL-2: PUS/Neuro = 7.3613E-9; PUS/Sham = 3.8765E-9; PNeuro/Sham = 0.427984. IL-10: PUS/Neuro = 1E-6; PUS/Sham = 1.5141E-7; PNeuro/Sham = 0.079821. H&E: PUS/Neuro = 2E-6; PUS/Sham = 6.8169E-8; PNeuro/Sham = 0.019865. n Representative colon pictures for US alone, NeuroRing, and sham control. o Average splenic weight and colon length calculated in the different groups. Splenic weight: PUS/Neuro = 2.8504E-9; PUS/Sham = 7.6726E-10; PNeuro/Sham = 0.087571. Colon length: PUS/Neuro = 1.8128E-9; PNeuro/Sham = 0.012544. p, q Average body weight (p) and DAI scores (q) over time calculated from different groups. Unless otherwise stated, all samples were collected on day 7 after the US intervention. All data are expressed as mean values ± SD. All error bars indicate ± SD. n = 5 biologically independent animals for each group. *P < 0.05, **P < 0.01, ***P < 0.001; ns, not significant. All P values are evaluated through one-sided ANOVA and post-Tukey analysis.