Lung Fixation under Constant Pressure for Evaluation of Emphysema in Mice

Karasutani, Keiko; Baskoro, Hario; Satô, Tadashi; Arano, Naoko; Suzuki, Yohei; Mitsui, Aki; Shimada, Naoki; Kodama, Yuzo; Seyama, Kuniaki; Fukuchi, Yoshinosuke; Takahashi, Kazuhisa

doi:10.3791/58197

Cited by 4 publications

(4 citation statements)

References 21 publications

(44 reference statements)

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“…Following euthanasia, the peritoneal cavity and rib cage were opened, and the lungs and trachea were isolated and weighed. The lungs were perfused and inflated using an intratracheal injection of 1× phosphate buffered saline (PBS) as previously described [41,42]. A 1mL syringe filled with PBS was inserted into the trachea and used to inflate the left lobe of the lung.…”

Section: Euthanasia and Collection Of Tissuementioning

confidence: 99%

A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice

Rumph

Rayford

Stephens

et al. 2021

Toxics

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New bronchopulmonary dysplasia is a developmental lung disease associated with placental dysfunction and impaired alveolarization. Risk factors for new BPD include prematurity, delayed postnatal growth, the dysregulation of epithelial-to-mesenchymal transition (EMT), and parental exposure to toxicants. Our group previously reported that a history of paternal toxicant exposure increased the risk of prematurity and low birth weight in offspring. A history of paternal toxicant exposure also increased the offspring’s risk of new BPD and disease severity was increased in offspring who additionally received a supplemental formula diet, which has also been linked to poor lung development. Risk factors associated with new BPD are well-defined, but it is unclear whether the disease can be prevented. Herein, we assessed whether a paternal fish oil diet could attenuate the development of new BPD in the offspring of toxicant exposed mice, with and without neonatal formula feeding. We investigated the impact of a paternal fish oil diet preconception because we previously reported that this intervention reduces the risk of TCDD associated placental dysfunction, prematurity, and low birth weight. We found that a paternal fish oil diet significantly reduced the risk of new BPD in neonatal mice with a history of paternal toxicant exposure regardless of neonatal diet. Furthermore, our evidence suggests that the protective effects of a paternal fish oil diet are mediated in part by the modulation of small molecules involved in EMT.

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Section: Euthanasia and Collection Of Tissuementioning

confidence: 99%

A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice

Rumph

Rayford

Stephens

et al. 2021

Toxics

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“…30 Here, we show that regional atelectasis can make both scoring and quantitative image analysis less consistent, but the effects of over-distension on quantitative image analysis have not been explored. 10,17,20,29 The development of standardized tissue collection, processing, and analysis techniques for SARS-CoV-2 studies using the hamster and mouse models will greatly improve comparison and interpretation of cross-institutional vaccine and therapeutic studies. With the rapid spread and reports of variable pathogenicity of the B.1.1.529 (Omicron) variants in the hamster model, 6,22,28 we propose a method for combined virology assessment and formalin instillation of lung for improved detection of lesions and virus for SARS-CoV-2 research.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments

Piedra-Mora

Robinson

Tostanoski³

et al. 2022

Vet Pathol

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There is a need to standardize pathologic endpoints in animal models of SARS-CoV-2 infection to help benchmark study quality, improve cross-institutional comparison of data, and assess therapeutic efficacy so that potential drugs and vaccines for SARS-CoV-2 can rapidly advance. The Syrian hamster model is a tractable small animal model for COVID-19 that models clinical disease in humans. Using the hamster model, the authors used traditional pathologic assessment with quantitative image analysis to assess disease outcomes in hamsters administered polyclonal immune sera from previously challenged rhesus macaques. The authors then used quantitative image analysis to assess pathologic endpoints across studies performed at different institutions using different tissue processing protocols. The authors detail pathological features of SARS-CoV-2 infection longitudinally and use immunohistochemistry to quantify myeloid cells and T lymphocyte infiltrates during SARS-CoV-2 infection. High-dose immune sera protected hamsters from weight loss and diminished viral replication in tissues and reduced lung lesions. Cumulative pathology scoring correlated with weight loss and was robust in distinguishing IgG efficacy. In formalin-infused lungs, quantitative measurement of percent area affected also correlated with weight loss but was less robust in non-formalin-infused lungs. Longitudinal immunohistochemical assessment of interstitial macrophage infiltrates showed that peak infiltration corresponded to weight loss, yet quantitative assessment of macrophage, neutrophil, and CD3+ T lymphocyte numbers did not distinguish IgG treatment effects. Here, the authors show that quantitative image analysis was a useful adjunct tool for assessing SARS-CoV-2 treatment outcomes in the hamster model.

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“…Mouse lungs were processed as described previously (20). The lungs were lavaged twice with 1 mL of PBS through an intratracheal cannula.…”

Section: Evaluation Of Bronchoalveolar Lavage Fluid and Lung Morphologymentioning

confidence: 99%

miR-146a regulates emphysema formation and abnormal inflammation in the lungs of two mouse models

Yoshikawa,

Sato,

Horikoshi

et al. 2024

American Journal of Physiology-Lung Cellular and Molecular Phys

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miR-146a, a microRNA (miRNA) that regulates inflammatory responses, plays an important role in many inflammatory diseases. Although an in vitro study had suggested that miR-146a is involved in abnormal inflammatory response, being a critical factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), in vivo evidence of its pathogenic role in COPD remains limited. Eight-week-old male B6(FVB)-Mir146tm1.1Bal/J (miR-146a knockout [KO]) and C57BL/6J mice were intratracheally administered elastase and evaluated after 28 d or exposed to cigarette smoke (CS) and evaluated after 5 months. miR-146a expression was significantly increased in C57BL/6J mouse lungs due to elastase administration ( P = 0.027) or CS exposure ( P = 0.019) compared with that in the control group. Compared with C57BL/6J mice, elastase-administered miR-146a-KO mice had lower average computed tomography (CT) values ( P = 0.017) and increased lung volume-to-weight ratio ( P = 0.016), mean linear intercept ( P < 0.001), and destructive index ( P < 0.001). Moreover, total cell ( P = 0.006), macrophage ( P = 0.001), neutrophil ( P = 0.026), chemokine (C-X-C motif) ligand 2/macrophage inflammatory protein-2 ( P = 0.045; in bronchoalveolar lavage fluid [BALF]), cyclooxygenase-2, and matrix metalloproteinase-2 levels were all increased (in the lungs). Following long-term CS exposure, miR-146a-KO mice showed a greater degree of emphysema formation in their lungs and inflammatory response in the BALF and lungs than C57BL/6J mice. Collectively, miR-146a protected against emphysema formation and the associated abnormal inflammatory response in two murine models.

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Lung Fixation under Constant Pressure for Evaluation of Emphysema in Mice

Cited by 4 publications

References 21 publications

A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice

A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments

miR-146a regulates emphysema formation and abnormal inflammation in the lungs of two mouse models

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