Axonal Necrosis of Enteric Autonomic Nerves in Continent Heal Pouches Possible Implications for Pathogenesis of Crohnʼs Disease

Dvorak, Ann M.; Onderdonk, Andrew B.; McLeod, Robin S.; Monahan-Earley, Rita A.; Cullen, Jim; Antonioli, Donald A.; Blair, J. E.; Morgan, Ellen S.; Cisneros, Ronald L.; Estrella, Patricia; Cohen, Zane; Silen, William

doi:10.1097/00000658-199303000-00008

Cited by 58 publications

(43 citation statements)

References 26 publications

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“…The ultrastructural pathology of this encoded study yielded im p o rta n t information related to mast cell and ba sophil biology [14,15], to the pathology of the enteric au tonomic nervous system [16], and to eosinophil biology, which we report here. Specifically, a subset of intestinal biopsies, showing eosinophil secretion by granule extru sion, was identified and correlated with specific disease, particular clinical study group, biopsy site, axonal necrosis (AN), bacterial cultures of replicate tissue biopsies, and specific bacterial isolates.…”

Section: Introductionmentioning

confidence: 88%

“…After all samples were examined and bacterial cultures (n = 91) accompanying them were completed, the entire study was uneoded, and clinical, histological, ultrastructural [13][14][15][16], and bacterial culture 1131 data were evaluated. Statistics were done using a x: analysis; p < 0.05 or less was used as a significant difference between groups tested when sufficient case numbers allowed such analysis.…”

Section: Methodsmentioning

confidence: 99%

“…We have completed an encoded clinical, endoscopic, light microscopic, bacteriologic, and electron microscopic study of 117 intestinal biopsies obtained from tissue sites in patients with ulcerative colitis (UC), Crohn's disease (CD), familial polyposis (FP) and neoplasia remote from areas that were grossly involved with these diseases and often in patients from whom all primary disease had been removed [13][14][15][16], Biopsy sites included tissues obtained from the ileum, colon and rectum (controls), as well as biopsies of conventional ileostomy stomas. Continent pouch biopsies (Kock [17] and pelvic varieties [18]) were obtained from patients for whom all clinical and endo scopic data were normal and from those with criteria for the clinical diagnosis of pouchitis -a complication of un certain etiology that occurs in some continent pouches [19][20][21],…”

Section: Introductionmentioning

confidence: 99%

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Ultrastructural Identification of Exocytosis of Granules from Human Gut Eosinophils in vivo

Dvorak

Onderdonk²,

McLeod³

et al. 1993

Int Arch Allergy Immunol

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Twenty-two percent of 117 biopsies of human intestinal tissues had ultrastructural images of classical regulated secretion from eosinophils in vivo i.e. eosinophil granule extrusion (EGE). Replicate intestinal biopsies that were positive for bacteria had EGE more often than not (p < 0.05); 77% of the isolates were Staphylococci. Some of the intestinal biopsies also had damaged nerves; all that had EGE and damaged enteric nerves also had positive bacterial cultures. The EGE that we observed could not account for all enteric nerve damage, suggesting multifactorial mechanisms for nerve damage in gut tissues. Among the possibilities are release of neurotoxic eosinophil granule proteins by an alternate secretory route, i.e., piecemeal degranulation, direct toxicity of tissue invasive bacteria and/or damaged nerves of unknown etiology such as those that are regularly present in uninvolved tissues of patients with Crohn’s disease.

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Section: Introductionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ultrastructural Identification of Exocytosis of Granules from Human Gut Eosinophils in vivo

Dvorak

Onderdonk²,

McLeod³

et al. 1993

Int Arch Allergy Immunol

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“…The autonomic nervous system is altered both structurally and functionally in IBD; structural changes in autonomic nerves in the gut include changes in ganglia size and number as well as axonal necrosis (12). Up to 35% of patients with ulcerative colitis exhibit autonomic imbalance, with impaired parasympathetic function resulting in sympathetic dominance (24).…”

mentioning

confidence: 99%

The protective effect of the vagus nerve in a murine model of chronic relapsing colitis

Ghia¹,

Blennerhassett²,

El–Sharkawy³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

117

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Ghia J-E, Blennerhassett P, El-Sharkawy RT, Collins SM. The protective effect of the vagus nerve in a murine model of chronic relapsing colitis. Am J Physiol Gastrointest Liver Physiol 293: G711-G718, 2007. First published August 2, 2007; doi:10.1152/ajpgi.00240.2007.-The vagus nerve inhibits the response to systemic administration of endotoxin, and we have recently extended this observation to show that the vagus attenuates acute experimental colitis in mice. The purpose of the present study was to determine whether there is a tonic counterinflammatory influence of the vagus on colitis maintained over several weeks. We assessed disease activity index, macroscopic and histological damage, myeloperoxidase (MPO) activity, and Th1 and Th2 cytokine profiles in chronic colitis induced by administration of dextran sodium sulfate (DSS) in drinking water for three cycles during 5 days with 11 days of rest between each cycle (DSS 3, 2, 2%) in healthy and vagotomized C57BL/6 mice and in mice deficient in macrophage-colony stimulating factor (M-CSF). A pyloroplasty was performed in vagotomized mice. Vagotomy accelerated the onset and the severity of inflammation during the first and second but not the third cycle. Although macroscopic scores were not significantly changed, histological scores as well as MPO activity and colonic tissue levels of IL-1␣, TNF-␣, IFN-␥, and IL-18 but not IL-4 were significantly increased in vagotomized mice compared with shamoperated mice that received DSS. In control mice (without colitis), vagotomy per se did not affect any inflammatory marker. Vagotomy had no effect on the colitis in M-CSF-derived macrophage-deficient mice. These results indicate that the vagus protects against acute relapses on a background of chronic inflammation. Identification of the molecular mechanisms underlying the protective role of parasympathetic nerves opens a new therapeutic avenue for the treatment of acute relapses of chronic inflammatory bowel disease. vagotomy; chronic experimental colitis; inflammatory bowel disease; cytokine; macrophages INFLAMMATORY BOWEL DISEASES (IBD), including ulcerative colitis and Crohn's disease, are chronic inflammatory disorders of the gastrointestinal tract that result in significant morbidity. The pathogenesis of IBD is unknown but is thought to reflect an interaction of genetic and environmental factors; chronic inflammation results from immune dysregulation and an intolerance of commensal bacteria in the gut (25,34,35). Clinical observations also suggest that the nervous system influences the clinical course of IBD. This is supported by the beneficial effects of lidocaine (40) or nicotine (28) in at least a subset of IBD patients. More direct evidence of a neural modulation is from a case study in which spinal cord stimulation, a therapeutic strategy for treating neuropathic pain, induced relapses of ulcerative colitis (23).The autonomic nervous system is altered both structurally and functionally in IBD; structural changes in autonomic nerves in the gut include changes in ga...

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“…Cytokine production can be modulated by neurotransmitters, including those of the autonomic nervous system (31). The autonomic nervous system is altered both structurally and functionally in IBD; structural changes in autonomic nerves in the gut include changes in ganglia size and number, as well as axonal necrosis (18). Up to 35% of patients with ulcerative colitis exhibit autonomic imbalance with impaired parasympathetic function, resulting in sympathetic dominance (29).…”

mentioning

confidence: 99%

Vagus nerve integrity and experimental colitis

Ghia

Blennerhassett²,

Collins³

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Previous studies have identified a counterinflammatory vagal reflex in the context of endotoxic shock. We have extended this observation to show that the vagus confers protection against acute (5 days) colitis induced by dextran sodium sulfate (DSS) or by dinitrobenzene sulfonic acid (DNBS). We have shown that this is mediated via macrophages and involves the suppression of proinflammatory cytokines. In this study, we have examined whether the vagal integrity confers long-lasting protection by studying DNBS-and DSS-induced inflammatory responses in the colon at 9 to 61 days postvagotomy. The integrity of vagotomy was confirmed at all time points using CCK-induced satiety. As previously described in a DNBS and DSS model, vagotomy associated with the pyloroplasty increased all indices of inflammation. Vagotomy increased the disease activity index as well as the macroscopic and histological scores by 75 and 41%, respectively. In addition, myeloperoxidase (MPO) activity, serum levels of C-reactive protein (CRP), and colonic tissue levels of proinflammatory cytokine increased when colitis was induced 9 days postvagotomy. However, these increases in inflammatory indices were substantially diminished in mice with colitis induced 21, 33, and 61 days postvagotomy. This was accompanied by an increased production of interleukin-10, transforming growth factor-␤, Forkhead Box P3 (FOXP3) staining in colonic tissue, and serum corticosterone. These findings indicate that although vagal integrity is an important protective factor, other counterinflammatory mechanisms come into play if vagal integrity is compromised beyond 2 wk. vagotomy; HPA axis; inflammatory bowel disease; cytokine; Treg cell INFLAMMATORY BOWEL DISEASE (IBD) is a chronic intestinal inflammatory state and is considered the consequence of an aberrant immune response to luminal antigens (21). Tissue injury results from the release of inflammatory mediators, including acid metabolites and proinflammatory cytokines (41,43,48). In particular, increased secretion of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-␣ (TNF-␣) (5,20), are considered to be important for the exacerbation of IBD and constitute targets for therapy. Cytokine production can be modulated by neurotransmitters, including those of the autonomic nervous system (31). The autonomic nervous system is altered both structurally and functionally in IBD; structural changes in autonomic nerves in the gut include changes in ganglia size and number, as well as axonal necrosis (18). Up to 35% of patients with ulcerative colitis exhibit autonomic imbalance with impaired parasympathetic function, resulting in sympathetic dominance (29). Studies in animal models support the notion that autonomic imbalance contributes to the inflammatory drive in IBD. This is based on observations that the sympathectomy improves experimental colitis (33) and that administration of the parasympathomimetic nicotine improves colitis in animal models (19).Previously, prompted by the demonstration of a ...

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Axonal Necrosis of Enteric Autonomic Nerves in Continent Heal Pouches Possible Implications for Pathogenesis of Crohnʼs Disease

Cited by 58 publications

References 26 publications

Ultrastructural Identification of Exocytosis of Granules from Human Gut Eosinophils in vivo

Ultrastructural Identification of Exocytosis of Granules from Human Gut Eosinophils in vivo

The protective effect of the vagus nerve in a murine model of chronic relapsing colitis

Vagus nerve integrity and experimental colitis

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