Vagotomy Research Articles

Vagus nerve (VN) and spleen dysfunctions are often associated with obesity (Ob). Aim: We evaluated the effects of VN and spleen ablation on adiposity, metabolism, and insulin secretion in hypothalamic obese male rats. Methods: Ob was induced by neonatal subcutaneous injection of monosodium glutamate (4 g/kg). At 60 days of life, Ob animals were randomly distributed into four groups (n = 16 rats/group): sham operation (SHAM), vagotomy (VAG), splenectomy (SPL), and VAG + SPL. Body weight and food intake were monitored for 8 weeks postsurgery. Intraperitoneal glucose tolerance test (ipGTT) and intraperitoneal pyruvate tolerance test (ipPTT) were performed at 148 days of life, and VN activity was recorded at 150 days. After euthanasia (150 days), adiposity, plasma biochemical parameters, glucose-induced insulin secretion (GIIS), and cholinergic and adrenergic islet responsiveness were evaluated. The pancreas was submitted for histopathological analysis, and the protein content of OXPHOS and IL-10 was evaluated in isolated pancreatic islets. Results: Decreased VN activity was confirmed in the Ob-VAG groups, associated with lower visceral adiposity, triglycerides, and plasma insulin, together with improved insulin sensibility and pyruvate tolerance, compared to Ob-SHAM rats. Spleen absence reduced VN activity and cholinergic insulinotropic responses, with deleterious effects on the endocrine pancreas. Furthermore, Ob-VAG + SPL rats presented greater reductions in GIIS and more severe endocrine pancreas histopathology, compared to the Ob-SHAM group, without altered islet size or number or protein content of OXPHOS or IL-10. Conclusion: Vagal and splenic interactions contribute to glucose homeostasis control in hypothalamic obese rats, modulating insulin secretion and pancreas histology.

The effects of gallic acid and vagotomy on motor function, intestinal transit, brain electrophysiology and oxidative stress alterations in a rat model of Parkinson's disease induced by rotenone

This study aims to determine the effect of low-intensity focused ultrasound (LIFU) in ischemic heart failure (IHF) and explore the potential neuroimmune mechanism. Sprague-Dawley rats were subjected to ultrasound (US) with specific parameters, and electrocardiograms were recorded to analyze the effect of LIFU and/or vagal denervation on heart rate. Thereafter, myocardial infarction (MI) was induced by left anterior artery ligation, and LIFU was performed three times a day for 25 days after MI. Echocardiography, Masson staining, and ELISA were used to evaluate the effect of LIFU on the structure and function of the heart. Finally, ELISA, flow cytometry, qRT-PCR, and Western blot analysis were performed to determine the effect of LIFU on the inflammation and the expression of the cholinergic anti-inflammatory pathway (CAP)-related mediators. LIFU reduced heart rate in rats (control vs LIFU, P <.01), and vagotomy (VT) eliminated this effect of LIFU on heart rate (VT vs LIFU + VT, P >.01). LIFU-ameliorated IHF in terms of cardiac structure and function (MI vs MI + LIFU, P <.01), but VT abrogated the beneficial effect of LIFU (MI + VT vs MI + LIFU + VT, P >.01). After the treatment of LIFU, decreased levels of inflammatory cytokines, increased proportion of anti-inflammatory macrophages, and increased expression of CAP-related mediators (MI vs MI + LIFU, P <.01). LIFU ameliorates IHF whereas the CAP plays a promising role. LIFU has the potential to be a novel nonpharmacological and noninvasive therapy for the treatment of coronary artery disease and other cardiovascular diseases.

Obesity may be treated by bariatric procedures and is related to enterohormone release modulation. Nevertheless, a majority of commonly used surgical procedures have a significant impact on vagus nerve function by breaking the connections with its gastric branches. In the case of an intragastric balloon (BAL), this interaction is unclear. However, BAL-induced weight reduction is not long-lasting. Interestingly, this method has not been used in combination with vagotomy (VAG). Thus, we evaluated, for the first time, the short- and long-term effects of combined BAL and VAG using the animal-based translational model and compared these effects with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Wistar rats were fed a high-calorie diet for 8weeks to induce obesity before SG, RYGB, BAL + / - VAG. Animals' weight and eating behaviors were monitored weekly. After 90days, serum samples were collected to evaluate postprandial and fasting GLP-1, GIP, PYY, ghrelin, glucagon, insulin, leptin, and pancreatic polypeptide concentrations by fluorescent assay. VAG, SG, RYGB, and BAL + VAG significantly reduced body weight 30 and 90days after surgery. BAL alone induced temporal weight reduction observed after 30days, reversed after 90days. Calories intake was reduced at the first half of the observation period in all groups. Fluid intake was reduced in all groups except SG and BAL. Enterohormone profile for BAL + VAG was comparable to SG and RYGB but not BAL. VAG and BAL + VAG but not BAL alone maintain weight reduction, alimentary intake changes, and enterohormone release after long-term observation. VAG may improve the effectiveness of bariatric procedures for obesity treatment in clinical practice.

Amoebic liver abscess (ALA) is the main extra-intestinal complication caused by Entamoeba histolytica. Given the histological features of ALA in hamsters and the importance of the vagus nerve in the immune response, the aim of this study was to identify and analyze the major changes in ALA that are caused by a vagotomy. The changes found are related to inflammatory foci and abscess size, the type of collagen formed, and the number of trophozoites in lesions. Male hamsters were divided into three groups: Intact animals (IA) and those undergoing a false operation (SHAM) or a subdiaphragmatic vagotomy (VAG). In each group, E. histolytica trophozoites or culture medium (CM) were inoculated in hamsters by the intrahepatic route, and then euthanized at 6h, 12h, 24h, 48h, 4d or 7d post-infection. Initially the growth of the abscess was more rapid in the VAG group, but at day 7 it was faster in the IA and SHAM groups. VAG animals showed a higher quantity of type III collagen than the IA and SHAM groups. A larger number of amoebic trophozoites/mm² was observed up to day 4 in VAG hamsters (23.3±2.19) compared to IA (14.6±0.23) and SHAM (6.13±0.87) animals. This parameter decreased by day 7 in VAG (13.4±0.87) with respect to IA (24.7±1.47) and SHAM (21.7±1.48). The results show that a subdiaphragmatic vagotomy influenced the development of ALA in hamsters, suggesting a modification of the morphological structure of damaged hepatic tissue.

Objective To investigate the protecting effect and mechanisms of electroacupuncturing Zusanli(ST36) on pulmonary microvascular endothelial cell(PMVEC) of septic rat. Methods One hundred and eight male Sprague-Dawley rats were randomly divided into 6 groups(n=18): sham group(group Sham), sepsis group (group LPS), acupuncture non-acupoint stimulation group (group non-EA), bilateral electroacupuncture Zusanli group(group EA), bilateral cervical vagotomy after sepsis group (group VGX), bilateral cervical vagotomy thus electroacupunctureing Zusanli group (group VGX/EA). Abdominal aortic blood samples were taken 0.8 ml at 3, 6, 9 h to measure plasma tumor necrosis factor-α(TNF-α) expression level. Lung tissues were collected to investigate the expression of Src-suppressed C kinase substrate (SSeCKS) mRNA and E-selection mRNA. The pulmonary microvascular endothelial cells were observed by transmission electron microscope at 6 h after LPS exposure. Results The expression levels of TNF-α in plasma, as well as SSeCKS mRNA and E-selection mRNA expression levels in lung tissue were obviously higher in other groups than the expression levels of these molecules in group Sham (P 0.05). The expression levels of TNF-α, SSeCKS mRNA and E-selection mRNA in group EA were markedly lower than the expression levels in group LPS(P 0.05). Transmission electron microscopy observed EA at Zusanli distinctly reduced the dysfunction of microvascular endothelial cells. Conclusions Electroacupuncturing Zusanli can protect LPS induced PMVEC injury and exert protective effects via activation of cholinergic anti-inflammatory pathway (CAP). Key words: Zusanli; Electroacupuncture; Sepsis; Pulmonary microvascular endothelial cell

Objective To evaluate the effect of electric stimulation of vagus nerves on the expression of aquaporin-4 (AQP-4) in brain tissues of rats with endotoxemia. Methods Forty-eight adult male Sprague-Dawley rats, aged 2 months, weighing 200-250 g, were divided into 4 groups (n=12 each) using a random number table: sham operation group (S group), endotoxemia group (E group), vagus nerve transection group (VNT group) and vagus nerve transection plus vagus nerve stimulation group (VNT+ VNS group). The model of endoxemia was established by injection of lipopolysaccharide 10 mg/kg via the femoral vein of anesthetized rats.Left cervical vagotomy was performed at 30 min before injection of lipopolysaccharide in VNT and VNT+ VNS groups.In VNT+ VNS group, electric stimulation of the distal end of the left vagus nerve was performed immediately after the end of surgery.Stimulation parameters were as follows: current intensity 0.5 mA, pulse width 0.5 ms, frequency 20 Hz, once every 5 min, 30 s per time, lasting for 1 h. Blood samples were collected from the abdominal aorta at 6 h after establishment of the model, and then the rats were sacrificed and brains were removed.The level of IL-1β in plasma and brain tissues and content of AQP-4 in brain tissues were measured by enzyme-linked immunosorbent assay.The Evans blue (EB) content in brain tissues and brain water content were determined. Results Compared with S group, the levels of IL-1β in plasma were significantly increased, and the contents of IL-1β, AQP-4 and EB in brain tissues and brain water content were increased in E, VNT and VNT+ VNS groups (P 0.05). Conclusion The mechanism by which electric stimulation of vagus nerves reduces brain injury may be related to decreased content of AQP-4 in brain tissues of rats with endotoxemia. Key words: Vagus nerve; Electric stimulation therapy; Endotoxemia; Brain; Aquaporin 4

Objective To determine whether dexmedetomidine(Dex) preconditioning could provide cardioprotection against ischemia/reperfusion injury(I/RI) through vagus nerve in rats. Methods Fifty male SD rats, weighing 230-270 g, were randomly divided into five groups(n=10): sham operation (group S), group I/R, unilateral vagotomy(VG)+I/R(group V), Dex+I/R (group D), VG+Dex+I/R(group VD). Dex 1 μg/kg for 10 min and 0.7 μg·kg-1·h-1 for 15 min was infused via the jugular vein. I/R model was established with ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Serum levels of IL-6 and TNF-α were measured with ELISA. The mRNA expression of IL-6 and TNF-α in myocardium was assayed with real-time quantitative PCR(qPCR). The area in heart at risk of injury was marked with Evans Blue. The infarct size was stained with 2,3,5-triphenyltetrazolium chloride. Results Compared with group I/R, the mRNA and protein levels of IL-6 and TNF-α and the infarct size were significantly decreased in group D(P<0.05). Compared with group D, these parameters were significantly increased in group VD(P<0.05). Conclusions Dex preconditioning protects heart against I/RI in rats by alleviating inflammatory response through intact vagus nerve. Key words: Myocardial ischemia/reperfusion injury; Dexmedetomidine; Vagus nerve; Cholinergic anti-inflammatory pathway

Truncal vagotomy is a surgical procedure that functionally denervates and disconnects multiple organs, including the stomach, liver, gallbladder,

Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

Evaluation of Proximal Gastric Vagotomy During a 10-Year Period

Bezoars are collections of undigested materials that can accumulate in any part of the gastrointestinal (GI) tract with the stomach being the most frequent location. They could occur as a complication of gastric surgery, which creates a low acid environment, decreased peristalsis, and abnormal pyloric function. Vagotomy and Billroth resections are culprit surgeries even decades after the procedure. The clinical presentation varies from asymptomatic, a vague feeling of epigastric discomfort and bloating to gastric ulcerations from pressure necrosis and subsequent GI bleeding, or gastric outlet obstruction. Endoscopy is not only the diagnostic test of choice but also has the advantage of offering therapeutic interventions like fragmentation or dissolution. When conservative treatments and endoscopic approaches fail, surgical extraction is recommended. We describe a patient with a gastric bezoar 25 years after vagotomy and Billroth I in which the diagnosis was delayed due to atypical presentation. J Med Cases. 2016;7(1):1-4 doi: http://dx.doi.org/10.14740/jmc2310w

Abstract Background/aim: Cholinergic nerves have been shown to regulate gastric WNT/ß-catenin signaling in leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)-positive stem cells and have recently been implicated in gastric tumorigenesis. Denervation by local vagotomy or botulinum neurotoxin type A injection or the muscarinic acetylcholine receptor 3 antagonist limit gastric cancer growth. The aim of this study was to further unravel the metabolic pathways underlying the vagotomy-induced suppression of gastric tumorigenesis. Methods: Unilateral subdiaphragmatic truncal vagotomy (VT) was performed in wild-type (WT) and the INS-GAS mice, a genetic mouse model of spontaneous gastric cancer. Metabolic profiling and gene expression profiling in gastric tissues at 6 months post-surgery were performed using liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry, high resolution magic angle spinning NMR spectroscopy, and microarray gene expression (Illumina). Results: VT-induced suppression of tumorigenesis was manifested by reduced proliferation rate and increased apoptotic and autophagic signaling pathways, leading to reduced tumor size and prolonged survival. Principal component analysis showed four distinct clusters among 343 metabolic compounds: WT without VT, INS-GAS without VT, WT with VT and INS-GAS with VT. In the gastric tumor, the metabolic pathways that regulate stem cell homeostasis were downregulated after VT. Glutaminolytic pathway, including glutamine, glutamate, glycine and glutathione-S-S-glutathione, was down-regulated. The tricarboxylic acid cycle (TCA), including citrate, cis-aconitate, acetyle-CoA, threonine and glycine, was also down-regulated. However, glycolytic pathway, including glucose, glucose 6-phosphate, fructose 6-phosphate and lactate, was not significantly down-regulated. Signaling pathways that regulate glutamine metabolism, such as WNT/ß-catenin signaling, WNT target genes Cyclin D1, Axin2, Myc, Lgr5 and Cd44, p53 signaling, and mTOR signaling were down-regulated. The central carbon metabolism in cancer (“The Warburg effect” signaling) and lactate production were unchanged after VT. In addition, the choline metabolism, the lipid-derived eicosanoids and prostaglandins were reduced after VT. Conclusions: The denervation-induced suppression of gastric tumorigenesis was associated with the inhibition of WNT/ß-catenin signaling-related glutamine metabolism but not the Warburg effect. We suggest that glutamine and choline phospholipid metabolisms can be used for metabolism-based tumor detection with MRS and/or positron emission tomography (PET) for gastric cancer diagnosis and that blocking these metabolic functions can be a therapeutic approach for gastric cancer treatment. Citation Format: Gøran Andersen, Riyas Vettukattil, Yoku Hayakawa, Jon Erik Grønbech, Timothy C. Wang, Duan Chen, Chun Mei Zhao. Inhibition of WNT/ß-catenin signaling-related glutamine metabolism but not the Warburg effect in denervation-induced suppression of gastric tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1167. doi:10.1158/1538-7445.AM2015-1167

To observe the effects of electrical stimulation of the vagus nerve on sepsis-associated encephalopathy, and to explore its possible mechanism. Forty adult male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, vagotomy group (VGX group), vagus nerve stimulation group (VNS group), with 10 rats in each group. The rat model of sepsis was reproduced by injecting lipopolysaccharide (LPS) through femoral vein, and rats of sham group were given the same volume of normal saline. The left cervical vagotomy was performed 30 minutes before LPS administration in VGX group, electrical stimulation of the left vagus nerve was initiated 30 minutes after LPS administration in VNS group. The rats in sham group were sacrificed after receiving electroencephalogram (EEG) examinations, and brain specimens were taken. The changes in EEG in the other three groups were monitored at 2, 4 and 6 hours after LPS administration, and the α wave activity percentage was calculated. The blood was collected from abdominal aorta 6 hours after LPS administration, the rats were sacrificed and brain tissue was harvested. The concentrations of tumor necrosis factor-α (TNF-α) in plasma and brain were measured with enzyme-linked immunosorbent assay (ELISA). The histology and ultrastructure changes in the prefrontal cortex in the rats were observed with both light microscope and transmission electron microscope. Compared with sham group, the percentage of α wave on EEG was significantly increased at 2, 4 and 6 hours after LPS administration in model group [(14.52±0.50)%, (16.70±0.85)%, (17.35±0.36)% vs. (12.60±0.46)%, all P<0.01]. It could be deduced that early brain dysfunction occurred in septic rats. Compared with model group, percentage of α wave on EEG was significantly reduced at 2, 4, and 6 hours in VNS group [(13.10±0.24)% vs. (14.52±0.50)%, (12.81±0.53)% vs. (16.70±0.85)%, (12.61±0.37)% vs. (17.35±0.36)%, all P<0.01], while there was no such effect in the VGX group. Compared with sham group, the concentrations of TNF-α in plasma and brain were all increased in model group [ plasma TNF-α(ng/L): 120.11±5.10 vs. 24.37±1.85, brain TNF-α(ng/L): 165.20±6.31 vs. 14.89±0.83, both P<0.01]. Compared with model group, the concentrations of TNF-α in plasma and brain were all significantly decreased in VNS group [ plasma TNF-α(ng/L): 46.72±4.90 vs. 120.11±5.10, brain TNF-α(ng/L): 107.95±1.83 vs. 165.20±6.31, both P<0.01], while there was no such effect in the VGX group. Light microscope and transmission electron microscope showed that the damage of brain tissue and neurons in model group and VGX group was more obvious, while that in the VNS group was less severe, though not completely disappeared. LPS can lead to sepsis-associated encephalopathy in rats. It was shown that electrical stimulation of the vagus nerve can activate anti-inflammatory effect through cholinergic pathway, and improve the cerebral function, and inhibit the development of sepsis-associated encephalopathy by reducing systemic and cerebral inflammatory reaction.

Safe surgery is founded upon accurate knowledge of the appropriate anatomy. The purpose of this book is to bring the latter into the operating theatre to describe operations principally in terms of the anatomy concerned. The second edition of this book describes the anatomy of general surgical operations in 44 chapters written by a variety of specialists in their fields, with all the chapters being co-authored by the main author. Although entitled ‘General Surgical Operations’, many of these operations would currently be undertaken in the UK by specialist surgeons, particularly those on the head and neck, neurosurgery and vascular surgery. Indeed, it is difficult to know what the definition of general surgery is at the present time, especially in the UK. The preface is very short and does not clearly indicate what the author considers to be the appropriate readership for the book. Certainly, many of the chapters are too advanced for those taking the MRCS but are eminently suitable for those taking the intercollegiate speciality FRCS in general surgery and equivalent examinations, in particular the Fellowship of the Royal Australasian College of Surgeons. The second edition has been totally redesigned with new art work and there is a greater coverage of the anatomical variation that the surgeon will encounter. There is also a greater accent on endoscopic procedures. The book is divided into seven parts – abdominal operations, general surgical operations in the thorax, head and neck surgery, surgical oncological procedures, arterial and venous surgery, general surgical neurological operations and surgery of the skin. Chapter 9, which describes the various forms of vagotomy, is a little dated but is of historical interest with the authors indicating that this operation is rarely undertaken nowadays. I particularly enjoyed reading chapter 15, which gives an exceptionally clear and practical approach to the anatomy of the anal canal. There were one or two inaccuracies in the book. For example, Figure 1.4 is not very clear and is poorly labelled (surely the first part of the figure should be labelled ‘rectus sheath – above the costal margin’). Also the third part of the figure should refer to the internal rather than external oblique aponeurosis while the word aponeurosis is also misspelt. In addition, some of the figures are unclear especially Figure 21.3, which is poorly drawn and at one point incorrectly labelled. Figure 23.1 is also unclear and poorly labelled. There is also some lack of consistency; in Chapter 21, Figure 21.4 contains the Latin nomenclature of muscles. In Chapter 36, the abdominal aorta is described as passing through the aortic hiatus in the diaphragm. Strictly speaking, there is no aortic hiatus in the diaphragm as the aorta passes behind the crura of the diaphragm in an osseoaponeurotic opening between the vertebral column and the diaphragm and, therefore, clearly behind the latter. In Chapter 37, the external iliac artery is described as crossing behind the mid-point of the inguinal ligament rather than the mid-inguinal point. Apart from these minor criticisms this is an excellent book describing the anatomical basis for general surgical operations. It is clearly written and the majority of the diagrams are excellent. Being written by surgeons it accentuates the important aspects of applied anatomy, giving sound practical advice. The problem is to whom would I recommend this book in the UK? Certainly, I would recommend it to those studying for the intercollegiate speciality examination in general surgery. Many of the chapters are probably too advanced for those studying for the MRCS. More experienced surgeons will also find it useful as a source of reference that clearly demonstrates the practical application of anatomy to the art of surgery.

Laparoscopic surgery is one of the key diagnostic and therapeutic tools in the current surgical era. 1 It is a principle technique for minimally invasive surgery, and has been used in procedures ranging across various surgical subspecialities. 2 Recent technological advances have enabled major progress and extension of the technique from gynaecologic surgery to major general surgical procedures. The greatest clinical advantages are probably in the area of abdominal general surgery, which is the main focus of this article. 3 Since the first laparoscopic cholecystectomy performed in the late 1980's, the technique has developed as the treatment of choice for patients with gallstone disease. It has also been applied to various thoracic, upper and lower abdominal procedures including fundoplication, vagotomy, hemicolectomy, herniorrhaphy, nephrectomy, pelvic lymph node dissection, bariatric surgery, hysterectomy and oesophagectomy, to name a few. 4

Objective To investigate the effect of bilateral cervical vagotomy on microglial activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR). Methods Thirty six male Sprague-Dawley rats were randomly divided into three groups (n= 12 each group): group sham operation, group SMIR, and group SMIR+ bilateral cervical vagotomy (SV). The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatter. Pain behavior was assessed by paw mechanical withdrawal threshold (MWT) to von Frey filament stimulation at 1, 3, and 5 days after operation. Four animals were sacrificed at each time point in each group to detect the expression of Iba-1 (a specific marker of microglia) in the spinal dorsal horn with immunofluorescence and the microglia was counted. Results MWT was significantly decreased at T1-5 in SMIR and SV (10.3±0.6, 9.7±0.8, 9.6±0.5; 8.0±0.7, 7.7±0.4, 7.6±0.3), while the expression of Iba-1 and microglia counts in the spinal dorsal horn were significantly increased at T1-5 in SMIR and SV (1428±134, 1245±129, and 1001±117; 8.0±0.7, 7.7±0.4, and 7.6±0.3; 187±13, 164±11, and 142±14; and 241±21, 230±21, and 202±19). In group SV as compared to group SMIR, MWT was significantly decreased at T1-5, while the expression of Iba-1 and microglia counts in the spinal dorsal horn were significantly increased at T1-5. Conclusions Vagus nerve plays an important role in microglial activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction. Key words: Vagotomy; Pain, postoperative; Microglia; Rats, Sprague-Dawley

Objective To study the effect of cutting vagus nerves on pathophysiology in dog model of acute necrotizing pancreatitis (ANP).Methods Twenty-six male adult hybrid dogs with good health were randomly divided into sham operation group (SG),control group (CG) and vagotomy group (VG).ANP model was induced by the retrograde injection of 5％ sodium taurocholate and trypsin into the pancreatic duct.The serum levels of pancreatic amylase (AMY),high-sensitivity C-reactive protein (HCRP),tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were monitored at different time-points after the operation,and then all the animals were sacrificed on postoperative day 7.The pancreas specimens were collected for pathological examinations,and histologic score were assessed.The dogs which died during the study period were recorded,and the causes of death were analyzed.Results There was no significant difference between these three groups on the level of serum AMY、HCRP、TNF-α and IL-10 before the operation (P ＞ 0.05).We found that the level of serum AMY、HCRP、TNF-a and IL-10 in CG group were increased compared with SG group after the success of the moulding.The levels of TNF-a and HCRP were significantly higher in VG than in CG group (P =0.001),but the level of IL-10 was lower than CG group (P =0.023).However,there was no significant difference between VG and CG in terms of the levels of serum AMY (P =0.158).Pancreatic histologic score of SG was the lowest,and pancreatic histologic score of VG was significantly higher than CG (P =0.03).Two dogs in CG group died in the experiment,four dogs in VG group died,and no death occurred in SG group.Conclusions The result implies the vagus nerve as a regulating role in the early stage of ANP.Cutting vagus nerves could exacerbate the development of ANP. Key words: Vagotomy; Acute necrotizing pancreatitis (ANP) ; Cytokines

Objective To investigate the effects of galantamine treatment on intestinal function in rats with sepsis.Methods Healthy male Sprague-Dawley(SD) rats were randomly divided into five experimental groups:Sham CLP group:rats were exposure abdominal cavity only.CLP group:cecal ligation and puncture (CLP) method to establish sepsis model.CLP+galantamine group:adminisration galantamine (5 mg/kg.ip) 1 h after CLP.vagotomy+CLP+galantamine group;right vagotomy 3 d before CLP.Sham vagotomy+CLP+galantamine group:Sham right vagotomy 3 d before CLP.Observed the survival rate of each group for 72 h.Rats were sacrificed at 12 h after CLP to observe the histopathological change of intestinal,and obtained the blood sample to test the endotoxin level,collected homogenated tissues of mesenteric lymph nodes,liver and spleen to determine bacterial translocation.Results The survival rate of rats in CLP group was significantly lower than in Sham CLP group (20％ vs 100％),and the serum endotoxin level and bacterial translocation were higher in CLP group than in Sham CLP group (61.1％ vs 11.1％,P＜0.05),galantamine administration could obviously decrease endotoxin level and bacterial translocation (27.8％ vs 61.1％,P＜0.05),however,vagotomy before CLP operation could abolish the protect effects of galantamine (27.8％ vs 61.1％,P＜0.05).Conclusions Galantamine can reduce the degree of intestinal mucosa damage and bacterial translocation,increase the survival rate.Activation of vagus nerve might coutribute to these effect. Key words: Sepsis; Galantamine; Intestinal mucosa barrier; Bacterial translocation; Cholinergic anti-inflammation pathway

Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus, leading to alteration of neurogenesis.