Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results

Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is involved in numerous pathophysiological conditions. Because PARP-1 knockout mice are resistant to endotoxininduced shock and inhibitors of the enzyme were reported to have similar beneficial properties, we investigated the effect of 4-hydroxyquinazoline (4-HQN), a potent PARP-1 inhibitor, on the modulation of kinase cascades and the regulation of transcription factors in a rodent septic shock model. T2-weighted magnetic resonance imaging showed the pattern of anatomical localization of the inflammatory response in bacterial lipopolysaccharide (LPS)-treated mice and the anti-inflammatory effect of the PARP-1 inhibitor. We have found that 4-HQN activated the phosphatidylinositol 3 (PI3)-kinase/Akt pathway in lung, liver, and spleen, and down-regulated two elements of the MAP kinase system. Namely, it dramatically attenuated the activation of the LPS-induced extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein (MAP) kinase in a tissue-specific manner. Furthermore, phosphorylation of p90RSK, a downstream target of ERK1/2, showed a similar pattern of down-regulation as did the phosphorylation of ERK1/2 and p38 after LPS and 4-HQN treatment. As a consequence of the aforementioned effects on the kinase pathways, 4-HQN decreased the activation of transcription factor nuclear factor-B (NF-B) and activator protein 1 (AP-1) in LPS-induced endotoxic shock. Our results provide evidence for the first time that the beneficial effects of PARP inhibition in endotoxic shock, such as attenuation of NF-B-and AP-1 transcription factor activation, are mediated, at least partially, through the regulation of the PI3-kinase/Akt pathway and MAP kinase cascades.

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“…Agreement between MRI data and histopathology was found to be satisfactory for acute local infection in mouse muscle (Ruiz-Cabello et al, 2002).…”

Section: Methodsmentioning

confidence: 86%

Regulation of Kinase Cascades and Transcription Factors by a Poly(ADP-Ribose) Polymerase-1 Inhibitor, 4-Hydroxyquinazoline, in Lipopolysaccharide-Induced Inflammation in Mice

Veres¹,

Radnai²,

Gallyas³

et al. 2004

J Pharmacol Exp Ther

118

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“…For a nephritis model, 1.0 × 10 3 spores were injected into the intra-medullar kidney (Walzl et al, 1987; Schaude et al, 1990). Cutaneous abscesses were generated in murine soft tissues by sc injections, mainly into the thigh after fur removal (Lupetti et al, 2002; Ruiz-Cabello et al, 2002; Donat et al, 2012), or by intradermal injections into the ears (Petersen et al, 2002; Goebel et al, 2005; Stein et al, 2013). …”

Section: Resultsmentioning

confidence: 99%

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Désoubeaux

Cray

2017

Front. Microbiol.

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Invasive aspergillosis has been studied in laboratory by the means of plethora of distinct animal models. They were developed to address pathophysiology, therapy, diagnosis, or miscellaneous other concerns associated. However, there are great discrepancies regarding all the experimental variables of animal models, and a thorough focus on them is needed. This systematic review completed a comprehensive bibliographic analysis specifically-based on the technical features of rodent models infected with Aspergillus fumigatus. Out the 800 articles reviewed, it was shown that mice remained the preferred model (85.8% of the referenced reports), above rats (10.8%), and guinea pigs (3.8%). Three quarters of the models involved immunocompromised status, mainly by steroids (44.4%) and/or alkylating drugs (42.9%), but only 27.7% were reported to receive antibiotic prophylaxis to prevent from bacterial infection. Injection of spores (30.0%) and inhalation/deposition into respiratory airways (66.9%) were the most used routes for experimental inoculation. Overall, more than 230 distinct A. fumigatus strains were used in models. Of all the published studies, 18.4% did not mention usage of any diagnostic tool, like histopathology or mycological culture, to control correct implementation of the disease and to measure outcome. In light of these findings, a consensus discussion should be engaged to establish a minimum standardization, although this may not be consistently suitable for addressing all the specific aspects of invasive aspergillosis.

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“…While MRI is widely used in humans to detect sites of infection, primarily in the brain, its use in infected mice has so far remained limited. There are few reports describing the visualization of inflammation in Staphylococcus aureus‐ , Aspergillus nidulans‐ or Candida albicans ‐infected muscles (Marzola et al ., 1999; Ruiz‐Cabello et al ., 1999; 2002), of cardiomyopathy in experimental chronic Trypanosoma cruzi infection (Huang et al ., 1999; 2002; Jelicks et al ., 1999; 2002a,b; De Souza et al ., 2003; 2004) or brain lesions in Theiler's virus or scrapie‐infected animals (Sadowski et al ., 2003; Pirko et al ., 2004a,b). However, its use in research to detect and monitor bacterial lung infection is only beginning.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of Klebsiella pneumoniae-induced pneumonia in mice

Tournebize

Doan²,

Dillies

et al. 2006

Cell Microbiol

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SummaryIn vivo imaging of small animals is a rapidly developing field. However, the potential of global imaging of infectious processes in animal models remains poorly explored. We used magnetic resonance imaging (MRI) to follow the development and regression of inflammatory lesions caused by infection by Klebsiella pneumoniae in mouse lungs. A virulent strain caused an intense inflammation within 2 days in the whole lungs, while an avirulent strain did not show significant changes. Mice infected with the virulent strain and subsequently treated with antibiotics presented a severe inflammation localized mainly in the left lung that disappeared after a week. The lesions observed by MRI correlated with the damage seen by histological analysis and a 3D representation of the tissue allowed better visualization of the development and healing of inflammatory lesions. MRI thus represents a powerful technique to study in vivo the interactions between a pathogen and its host in real time.

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Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results

Cited by 15 publications

References 34 publications

Regulation of Kinase Cascades and Transcription Factors by a Poly(ADP-Ribose) Polymerase-1 Inhibitor, 4-Hydroxyquinazoline, in Lipopolysaccharide-Induced Inflammation in Mice

Regulation of Kinase Cascades and Transcription Factors by a Poly(ADP-Ribose) Polymerase-1 Inhibitor, 4-Hydroxyquinazoline, in Lipopolysaccharide-Induced Inflammation in Mice

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Magnetic resonance imaging of Klebsiella pneumoniae-induced pneumonia in mice

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