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The paper reviews recent advances in vagal nerve stimulation for the control of food intake and body weight. The vagal nerves are the predominant pathway in the "brain-gut axis" responsible for short term regulation of food intake. Stimulation of afferent vagal traffic attenuates food intake by vagal projections to nucleus tractus solitarius, arcuate nucleus and its convergence’s to thalamic center of satiety. A few studies have been published in this field so far. All of them are consistent and show significant decrease in body mass during vagal stimulation. Due to promising results of experimental studies, clinical trials are expected in the near future.
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Encoding meal in integrated vagal afferent discharge

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Vagal afferents are integral part of the negative feedback loop induced by constitution and size of food stomach and jejunum. Aim of this study was to assess vagal discharge in response to food and gastric distension in rats. Electrophysiological recordings of vagal afferents in fasted (n=32), fed rats (n=20) and during gastric balloon distension (n=12) were performed. After 60 minutes of fasted nerve recording tube feeding was done. Fasted rats also underwent gastric distension via oesophagus. Vagal afferents discharges were analysed with dual time-amplitude window discriminator. Total vagal afferent discharge in fasted and fed rats revealed 0.3 ± 0.12 vs 0.56 ± 0.22 Hz (p<0.05). We observed two distinct discharge patterns: high amplitude low frequency (HALF) and low amplitude high frequency (LAHF). HALF spikes were observed more frequent in fasted than in fed rats (0.05 ± 0.02 vs. 0.03 ± 0.016 Hz (p<0.05). Conversely LAHF spikes in fed rats predominated over their occurrence in fasted rats: 0.52 ± 0.2 vs. 0.25 ± 0.12 Hz (p<0.05). Left vagal afferents discharge rises with gastric distension of 6, 8 and 10 ml and were: 0.46 ± 0.22 Hz, 0.65 ± 0.31 Hz, 0.86 ± 0.33 Hz (p<0.05) respectively. Similar discharge showed right vagal afferents: 0.41 ± 0.08 Hz, 0.51 ± 0.13 Hz and 0.77 ± 0.27 Hz (p<0.05) for 6, 8 and 10 ml of distension, respectively. We conclude that interdigestive information from gastrointestinal tract is encoded in high amplitude low frequency of spikes pattern in the vagus nerves.
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It is hypothesised that the GABA(B) receptor agonist baclofen increases or has no effect on food intake, and electrical stimulation of vagal nerves decreases food intake. The aim of this study was to evaluate the effects of baclofen in vagally stimulated rats. Material and methods: Thirty two Wistar rats were divided into five groups: group A scheduled for microchip implantation for vagal stimulation, group B for sham operation, group C for microchip implantation and baclofen medication, group D for baclofen medication only and group E for gastric motility evaluation under influence of baclofen. The following parameters were then evaluated: food intake and body mass, gastric motility, leptin, insulin, and glucose serum levels. Results: In the comparison of groups B and A, daily food intake and body weight gain decreased by 17% (p<0.05) and by 22% (p<0.05), respectively. Baclofen alone (group D) did not significantly change either food intake nor diurnal body weight compared to the controls, but when used in conjunction with the microchip (group C) it did significantly reduce effect of vagal neuromodulation (p<0.05). Furthermore, a significant decrease in leptin and glucose levels was detected in group C: 677 to 165 pg/ml (p<0.05) and 5,93 to 4,88 mmol/l (p<0.05), respectively. The administration of baclofen stimulated significantly gastric motility and elicited irregular motor migrating complex (327±200 against control 255±52 cmH2O/s). Conclusions: These results suggest that microchip vagal neuromodulation through increased vagal afferent activity induces an alteration in the feeding behaviour and decreases nocturnal food intake and body weight. These effects were partially attenuated by baclofen. The data suggests that GABA(B) receptors play an important role in the pathomechanism of attenuation of food intake induced by vagal nerve stimulation.
Food induced neurohumoral signals are conduced to data processing brain centers mainly as vagal afferent discharge resulting in food intake regulation. The aim of this study was to evaluate effects of vagal nerve neuromodulation in control of food intake with fed-pattern microchip (MC) pacing. Experiments were performed on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was combined with right side abdominal vagotomy. Body weight and total food intake decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV), 38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation on final body weight and food intake was significantly more effective than only single nerve MC pacing however most effective was stimulation with 0,1Hz combined with right vagotomy. We conclude that vagal stimulation reduce food intake and body weight by increasing vagal afferent signals. Our results suggest that information in vagal afferents can be modulated resulting in changes of feeding behaviour and body weight.
Afferent fibers from gastrointestinal tract outnumber efferents ten times in vagal nerves. Modifying the afferent input makes possible to change discharge of vagal efferents affecting gastrointestinal functions in process known as neuromodulation (NM). Lately it has been used in the treatment of pain and hyperactive neurogenic bladder in urology. MC induced NM may therefore provide a concurrent to pharmacology tool, in treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of long term neuromodulation procedure with use of MC on gastric motility, secretion and weight control in conscious rats. Experiments were performed on 30 Wistar male rats (250—350 g) divided in two groups: sham operated and microsurgically implanted with MC on left vagal nerve below diaphragm. Following stimulation parameters were used: frequency of 0.5—30 Hz, amplitude of 0.55 V, impulse duration of 10 ms in monophasic fashion. In both groups food intake and body weight were measured through the period of 2 weeks after recovery period. Then gastric fistula was implanted in gastric antrum and fasted gastric motility recorded with use of PowerLab system (Australia). Gastric emptying and secretion were also tested with use of phenol red and automatic titration methods. On the daily basis glucose level with standard test and leptin after MC implantation were measured. Recording of vagal activity in fasted rats showed burst of action potentials about 5 ± 2,5 in period of 5000 sec, each burst with spike frequency up to 35 Hz. Food (5 ml of Intralipid – intragastrically) almost doubled amount of bursts to 12 ± 5 in period of 5000 sec with increase in frequency at spike up to 50 Hz. MC induced vagal activity showed continuous spike activity similar to fed pattern. MC induced NM decreases daily food intake by 6% (33.6 ± 4.8 vs control 35.5 ± 4.8 g, p < 0.01). Body weight gain in rats before MC implantation decreased by 20% within 2 weeks after recovery (34.8 ± 9.08 vs control 23.56 ± 4.15 g). Fasting control glucose level also decreased of 5.5% (93.15 ± 9.3 vs control 98.5 ± 11.2 mg%, p < 0.05). Frequency of gastric contractions did not change significantly in MC versus control but amplitude of contractions increased of about 66.7% (2.0 ± 0.8 vs 1.17 ± 0.52) at the dominant frequency 0.08 Hz range and about 71.5% (1.17 ± 0.35 vs 0.68 ± 0.47, p < 0.05) at the frequency 0.12 Hz. in FFT analysis PowerLab (chart v = 4.01). BAO decreased by 29.25% without H+ concentration changes (0.2 ± 0.14 vs 0.14 ± 0.12 mmol/30min, p < 0,05) but MAO did not change in MC rats (0.37 ± 0.25 vs 0.42 ± 0.28 mmol/30min, p0.05). Gastric emptying of isotonic solution increased by 10% (90.46 ± 5.34 vs 80.39 ± 9.95) percent of marker passing to duodenum /5min,.p < 0.0001). Our results suggest that MC induced NM affect brain-gut axis via influencing metabolic and gastric function and decreases body weight. 706
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