Assessment of colon and bladder crosstalk in an experimental colitis model using contrast‐enhanced magnetic resonance imaging

Abstract

Background Inflammatory bowel disease (IBD) consists of two chronic remitting-relapsing inflammatory disorders in the colon referred to as ulcerative colitis (UC) and Crohn’s disease (CD). IBD affects about 1.4 million Americans. TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced colitis is a widely used model of experimental intestinal inflammation with characteristic transmural and segmental lesions that are similar to CD. Methods Here we report on the use of contrast-enhanced MRI (CE-MRI) to monitor in vivo bladder permeability changes resulting from bladder crosstalk following colon TNBS exposure, and TNBS-induced colitis. Changes in MRI signal intensities and histology were evaluated for both colon and bladder regions. Key Results Uptake of contrast agent in the colon demonstrated a significant increase in signal intensity (SI) for TNBS-exposed rats (p<0.01) compared to controls. Additionally, a significant increase in bladder SI for colon TNBS-exposed rats (p<0.001) was observed compared to saline controls. Histological damage within the colon was observed, however bladder histology indicated a normal urothelium in rats with TNBS-induced colitis, despite increased permeability seen by CE-MRI. Conclusions & Inferences CE-MRI was able to quantitatively measure inflammation associated with TNBS-induced colitis, as well as assess bladder crosstalk measured as an increase in urothelial permeability. Although CE-MRI is routinely used to assess inflammation with IBD, currently there is no diagnostic test to assess bladder crosstalk with this disease, and our developed method may be useful in providing crosstalk information between organ and tissue systems in IBD patients, in addition to colitis.

Inhibition of CXCR4 in Spinal Cord and DRG with AMD3100 Attenuates Colon-Bladder Cross-Organ Sensitization

“…Many previous studies have shown that the permeability of the bladder epithelium increases significantly after colon inflammation. 41 , 42 Mast cell activation has been proved to be a key factor, and mast cell stabilizers can reverse the increase in epithelial permeability. 22 The permeability change of the urothelium is an important cause of bladder pain and urination symptoms.…”

SuperGAG biopolymers for treatment of excessive bladder permeability

“…Two animal models were used. A rat model described in detail previously 25,[42][43][44][45] was used to confirm that the SuperGAG restores impermeability using the TEER "gold standard." This same model was used to confirm that restoring bladder impermeability abrogates the abdominal pain result.…”

“…Two animal models were used. A rat model described in detail previously 25,42‐45 was used to confirm that the SuperGAG restores impermeability using the TEER “gold standard.” This same model was used to confirm that restoring bladder impermeability abrogates the abdominal pain result. The restoration of impermeability also was confirmed in a transgenic mouse model that is receiving increasing acceptance as a model for IC/BPS 46 .…”

MRI as a Tool to Assess Interstitial Cystitis Associated Bladder and Brain Pathologies

“…Gd-DTPA normally does not go through an impermeable bladder wall. Of interest, we were also able to detect bladder-colon crosstalk associated colitis via intravenous (iv) administration of Gd-DTPA [ 28 ], as well as BWH from colon-bladder crosstalk following the induction of intestinal cystitis with trinitrobenzene sulfonic acid (TNBS) [ 38 ]. CE-MRI of BWH could therefore also be applied to assess colon–bladder crosstalk in inflammatory bowel disease (IBD) patients, as well as other inflammatory colon diseases.…”

“…Following the preclinical rat PS-induced BWH study, we then conducted a human pilot study comparing IC/BPS patients with normal individuals and clearly demonstrated the clinical feasibility of detecting BWH in IC/BPS [ 41 ]. Due to the increased thickness of the human bladder wall, BWH was detected within the bladder wall (see Figure 1 G–I where there was a significant increase in % difference in MRI SI for the IC bladders ( p < 0.001) compared to controls) [ 41 ] rather than the outside regions as seen in the preclinical models [ 28 , 38 , 39 ]. Another group used a mixture of both Gd-DTPA (Gadavist) and an iron oxide contrast agent, ferumoxytol, to further enhance bladder wall contrast in rats with induced cystitis (PS-induced) [ 42 ] and more recently in patients with IC [ 43 ].…”