Research Report
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World J Gastroenterol. Nov 28, 2014; 20(44): 16690-16697
Published online Nov 28, 2014. doi: 10.3748/wjg.v20.i44.16690
Alleviated mucosal and neuronal damage in a rat model of Crohn’s disease
Petra Talapka, Lajos István Nagy, Alexandra Pál, Marietta Zita Poles, Anikó Berkó, Mária Bagyánszki, László Géza Puskás, Éva Fekete, Nikolett Bódi
Petra Talapka, Alexandra Pál, Marietta Zita Poles, Anikó Berkó, Mária Bagyánszki, Éva Fekete, Nikolett Bódi, Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences and Informatics, University of Szeged, H-6726 Szeged, Hungary
Lajos István Nagy, László Géza Puskás, Avidin Ltd., Alsó kikötő sor 11, H-6726 Szeged, Hungary
Author contributions: Talapka P performed the majority of experiments and analyzed the data; Nagy LI and Berkó A performed the molecular investigations; Pál A, Poles MZ and Bódi N participated equally in treatment of animals; Bagyánszki M, Puskás LG, Fekete É and Bódi N designed and coordinated the research; Talapka P, Fekete É and Bódi N wrote the paper.
Supported by Hungarian Scientific Research Fund, No. OTKA PD 108309 (to Bódi N); and European Union and the State of Hungary; co-financed by the European Social Fund in the framework of TÁMOP 4.2.4.A/2-11/1-2012-0001 “National Excellence Program”
Correspondence to: Nikolett Bódi, PhD, Senior Lecturer, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary. bodiniki85@gmail.com
Telephone: +36-62-544149 Fax: +36-62-544291
Received: March 27, 2014
Revised: May 27, 2014
Accepted: July 22, 2014
Published online: November 28, 2014
Abstract

AIM: To establish a rat model suitable to investigate the repetitive relapsing inflammations (RRI) characteristic to Crohn’s disease.

METHODS: Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). RRI were mimicked by repeating administrations of TNBS. Tissue samples were taken from control, once, twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal inflammation. The means of the ulcerated area were measured to evaluate the macroscopic mucosal damage. The density of myenteric neurons was determined on whole mounts by HuC/HuD immunohistochemistry. Heme oxygenase-1 (HO-1) expression was evaluated by molecular biological techniques.

RESULTS: TNBS-treated rats displayed severe colitis, but the mortality was negligible, and an increase of body weight was characteristic throughout the experimental period. The widespread loss of myenteric neurons, and marked but transient HO-1 up-regulation were demonstrated after the first TNBS administration. After repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased, and the neuronal loss was on a smaller scale and was limited to the inflamed area. HO-1 mRNA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints examined. Nevertheless, the HO-1 protein up-regulation after the second TNBS treatment proved to be transient. Following the third treatment HO-1 protein expression could not be detected.

CONCLUSION: Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal damage. The persistent up-regulation of HO-1 mRNA expression may correlate with this.

Keywords: Crohn’s disease, Experimental rat model, Heme oxygenase-1, Myenteric neurons, Repetitive relapsing inflammation

Core tip: We report our first results derived from a newly developed rat model with chronic experimental colitis allowed us to modelling the recurring periods of recrudescence and remission in Crohn’s disease. Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Repetitive recurrent inflammations (RRI) were mimicked by repeated administrations of TNBS. This study demonstrates for the first time that experimentally provoked RRI develop preconditioning effect by speeding up mucosal healing and restoring myenteric neuronal injury. Decreased severity of gut inflammation after repeated TNBS treatments might be associated with the persistent up-regulation of heme-oxygenase 1 messenger RNA expression.