bioRxiv Science⌕ Search

Biology subjects

Vanoirbeek, J.

Publications and source records attributed to Vanoirbeek, J..

2 recordsLinked to original sources

Cardiopulmonary structural, functional and immune-alterations in a Down syndrome mouse model and upon modulation of EGCG

In individuals with Down syndrome (DS), cardiovascular and pulmonary diseases are the most common health problem and result in increased mortality and morbidity. Although these clinical comorbidities are well described, no preclinical models for DS are fully characterized for cardiopulmonary alterations, preventing research to understanding the development and pharmacological modulation of lungs, heart and immune system. Our objective is to characterize the cardiopulmonary and immunological phenotype in Ts65Dn mice and investigate the modulatory effects green tea extract enriched in epigallocatechin 3 gallate (GTE-EGCG). GTE-EGCG administration started at embryonic day 9 and was discontinued at postnatal day (PD) 180. Newborns were longitudinally monitored until PD210 using micro-computed tomography. At endpoint, we characterized the structural, functional and immunological alterations and persistent effects of GTE-EGCG administration. This study revealed normal lung development in the Ts65Dn mice and highlighted RV hypertrophy and immunological alterations. GTE-EGCG administration resulted in genotype-specific and genotype-independent alterations resulting in lung immaturation and airway hyperreactivity. Our results highlight the cardiovascular and immunological phenotype of Ts65Dn mice and potential use for safety studies of therapeutic agents in a DS-specific context. Summary statementThis study longitudinally follows respiratory and cardiac alterations in the Ts65Dn mouse model and describes the impact of prenatal EGCG modulation on the euploid and trisomic phenotype

systems biology↗

Radiosafe micro-computed tomography for longitudinal evaluation of murine disease models

Implementation of in vivo high-resolution micro-computed tomography (CT), a powerful tool for longitudinal analysis of murine lung disease models, is hampered by the lack of data on cumulative low-dose radiation effects on the investigated disease models. We aimed to measure radiation doses and effects of repeated CT scans, to establish cumulative radiation levels and scan protocols without relevant toxicity. Lung metastasis, inflammation and fibrosis models and healthy mice were weekly scanned over one-month with CT using high-resolution respiratory-gated 4D and expiration-weighted 3D protocols, comparing 5-times weekly scanned animals with controls. Radiation dose was measured by ionization chamber, optical fiberradioluminescence probe and thermoluminescent detectors in a mouse phantom. Dose effects were evaluated by in vivo CT and bioluminescence imaging read-outs, gold standard endpoint evaluation and blood cell counts. Weekly exposure to 4D CT, dose of 540-699 mGy/scan, did not alter lung metastatic load nor affected healthy mice. We found a disease-independent decrease in circulating blood platelets and lymphocytes after repeated 4D CT. This effect was eliminated by optimizing a 3D protocol, reducing dose to 180-233 mGy/scan while maintaining equally high-quality images. We established CT safety limits and protocols for weekly repeated whole-body acquisitions with proven safety for the overall health status, lung, disease process and host responses under investigation, including the radiosensitive blood cell compartment.

physiology↗