Morphofunctional Analysis of Experimental Model of Esophageal Achalasia in Rats

Sabirov, Alexey; Raginov, I. S.; Бурмистров, М В; Chelyshev, Y. A.; Хасанов, Р Ш; Морошек, А А; Grigoriev, P. N.; Зефиров, А. Л.; Mukhamedyarov, Marat A.

doi:10.1007/s10517-010-0972-6

Cited by 3 publications

(3 citation statements)

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“…Another achalasia model consists of local pharmacological denervation of the abdominal portion of the esophagus by wrapping the esophagus of albino rats with thick gauze soaked in the neurotoxin benzalkonium chloride. Apparent morphological and functional disorders were observed in the esophagus of this experimental achalasia model, correlating with changes in observed humans with achalasia [28,29]; another model involves the injection of benzyldimethyltetradecylammonium chloride into the distal esophagus of opossums to increase pressure in the lower esophageal sphincter; some of the histological observations resulting from this treatment resemble features of achalasia [30,31]. Furthermore, a report has shown that aged Rassf1a-deficient mice are more susceptible to megaesophagus than their wild-type littermates.…”

Section: Discussionsupporting

confidence: 55%

Docking Proteins Upregulate IL-1β Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia

Kanda,

Saiki,

Kurumi

et al. 2024

JCM

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Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results: DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1β and DOK1, IL-1β and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1β expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder.

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Section: Discussionsupporting

confidence: 55%

Docking Proteins Upregulate IL-1β Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia

Kanda,

Saiki,

Kurumi

et al. 2024

JCM

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“…The rat model of achalasia was successfully produced by injecting 0.2% BAC into the abdominal portion of the esophagus for ablation of the ganglion cells of the myenteric plexus. 33 Pathological changes were observed mainly in the middle and lower thirds of the esophagus, resulting in reductions in body weight and food intake, malnutrition and immune impairment. The animal model set up and treatment plan are summarized in Fig.…”

Section: Resultsmentioning

confidence: 99%

Poly(lactic acid)-hyperbranched polyglycerol nanoparticles enhance bioadhesive treatment of esophageal disease and reduce systemic drug exposure

et al. 2022

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“…4,28,48,68,69,73,79,88 Using gauze soaked with benzalkonium chloride (BAC) wrapped around the abdominal portion of the esophagus in rats, investigators demonstrated that the esophageal diameter was increased and the number of myenteric plexus neurons was reduced while the histological changes and contractile characteristics similar to that in humans with achalasia were noted. 28,68 One group successfully used this model to study preneoplastic lesions associated with achalasia. 82 BAC has also been successfully applied in the opossum 32,73 and dog.…”

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confidence: 99%

Megaesophagus in a Line of Transgenic Rats

et al. 2014

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Megaesophagus is defined as the abnormal enlargement or dilatation of the esophagus, characterized by a lack of normal contraction of the esophageal walls. This is called achalasia when associated with reduced or no relaxation of the lower esophageal sphincter (LES). To date, there are few naturally occurring models for this disease. A colony of transgenic (Pvrl3-Cre) rats presented with megaesophagus at 3 to 4 months of age; further breeding studies revealed a prevalence of 90% of transgene-positive animals having megaesophagus. Affected rats could be maintained on a total liquid diet long term and were shown to display the classic features of dilated esophagus, closed lower esophageal sphincter, and abnormal contractions on contrast radiography and fluoroscopy. Histologically, the findings of muscle degeneration, inflammation, and a reduced number of myenteric ganglia in the esophagus combined with ultrastructural lesions of muscle fiber disarray and mitochondrial changes in the striated muscle of these animals closely mimic that seen in the human condition. Muscle contractile studies looking at the response of the lower esophageal sphincter and fundus to electrical field stimulation, sodium nitroprusside, and L-nitro-L-arginine methyl ester also demonstrate the similarity between megaesophagus in the transgenic rats and patients with achalasia. No primary cause for megaesophagus was found, but the close parallel to the human form of the disease, as well as ease of care and manipulation of these rats, makes this a suitable model to better understand the etiology of achalasia as well as study new management and treatment options for this incurable condition.

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Morphofunctional Analysis of Experimental Model of Esophageal Achalasia in Rats

Cited by 3 publications

References 10 publications

Docking Proteins Upregulate IL-1β Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia

Docking Proteins Upregulate IL-1β Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia

Poly(lactic acid)-hyperbranched polyglycerol nanoparticles enhance bioadhesive treatment of esophageal disease and reduce systemic drug exposure

Megaesophagus in a Line of Transgenic Rats

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