36 research outputs found
Temporal and Spatial Analysis of Clinical and Molecular Parameters in Dextran Sodium Sulfate Induced Colitis
Background: Inflammatory bowel diseases (IBD), including mainly ulcerative colitis (UC) and Crohn’s disease (CD), are inflammatory disorders of the gastrointestinal tract caused by an interplay of genetic and environmental factors. Murine colitis model induced by Dextran Sulfate Sodium (DSS) is an animal model of IBD that is commonly used to address the pathogenesis of IBD as well as to test efficacy of therapies. In this study we systematically analyzed clinical parameters, histological changes, intestinal barrier properties and cytokine profile during the colitic and recovery phase. Methods: C57BL/6 mice were administered with 3.5 % of DSS in drinking water for various times. Clinical and histological features were determined using standard criteria. Myeloperoxidase (MPO) activity, transepithelial permeability and proinflammatory mediators were determined in whole colon or proximal and distal parts of colon. Results: As expected after administration of DSS, mice manifest loss of body weight, shortening of colon length and bloody feces. Histological manifestations included shortening and loss of crypts, infiltration of lymphocytes and neutrophil, symptoms attenuated after DSS withdrawal. The MPO value, as inflammation indicator, also increases significantly at all periods of DSS treatment, and even after DSS withdrawal, it still held at very high levels. Trans-mucosal permeability increased during DSS treatment, but recovered to almost control level after DSS withdrawal. The production of proinflammatory mediators by colonic mucosa were enhanced during DSS treatment, and then recovered to pre-treate
Cell Spatial Analysis in Crohn's Disease: Unveiling Local Cell Arrangement Pattern with Graph-based Signatures
Crohn's disease (CD) is a chronic and relapsing inflammatory condition that
affects segments of the gastrointestinal tract. CD activity is determined by
histological findings, particularly the density of neutrophils observed on
Hematoxylin and Eosin stains (H&E) imaging. However, understanding the broader
morphometry and local cell arrangement beyond cell counting and tissue
morphology remains challenging. To address this, we characterize six distinct
cell types from H&E images and develop a novel approach for the local spatial
signature of each cell. Specifically, we create a 10-cell neighborhood matrix,
representing neighboring cell arrangements for each individual cell. Utilizing
t-SNE for non-linear spatial projection in scatter-plot and Kernel Density
Estimation contour-plot formats, our study examines patterns of differences in
the cellular environment associated with the odds ratio of spatial patterns
between active CD and control groups. This analysis is based on data collected
at the two research institutes. The findings reveal heterogeneous
nearest-neighbor patterns, signifying distinct tendencies of cell clustering,
with a particular focus on the rectum region. These variations underscore the
impact of data heterogeneity on cell spatial arrangements in CD patients.
Moreover, the spatial distribution disparities between the two research sites
highlight the significance of collaborative efforts among healthcare
organizations. All research analysis pipeline tools are available at
https://github.com/MASILab/cellNN.Comment: Submitted to SPIE Medical Imaging. San Diego, CA. February 202
Targeted Deletion of Neuropeptide Y (NPY) Modulates Experimental Colitis
Neurogenic inflammation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). We examined the role of neuropeptide Y (NPY) and neuronal nitric oxide synthase (nNOS) in modulating colitis.Colitis was induced by administration of dextran sodium sulphate (3% DSS) or streptomycin pre-treated Salmonella typhimurium (S.T.) in wild type (WT) and NPY (NPY(-/-)) knockout mice. Colitis was assessed by clinical score, histological score and myeloperoxidase activity. NPY and nNOS expression was assessed by immunostaining. Oxidative stress was assessed by measuring catalase activity, glutathione and nitrite levels. Colonic motility was assessed by isometric muscle recording in WT and DSS-treated mice.DSS/S.T. induced an increase in enteric neuronal NPY and nNOS expression in WT mice. WT mice were more susceptible to inflammation compared to NPY(-/-) as indicated by higher clinical & histological scores, and myeloperoxidase (MPO) activity (p<0.01). DSS-WT mice had increased nitrite, decreased glutathione (GSH) levels and increased catalase activity indicating more oxidative stress. The lower histological scores, MPO and chemokine KC in S.T.-treated nNOS(-/-) and NPY(-/-)/nNOS(-/-) mice supported the finding that loss of NPY-induced nNOS attenuated inflammation. The inflammation resulted in chronic impairment of colonic motility in DSS-WT mice. NPY -treated rat enteric neurons in vitro exhibited increased nitrite and TNF-alpha production.NPY mediated increase in nNOS is a determinant of oxidative stress and subsequent inflammation. Our study highlights the role of neuronal NPY and nNOS as mediators of inflammatory processes in IBD