Rat model of smoke inhalation-induced acute lung injury

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

Download Full-text

The pre-term guinea-pig: a model for the study of neonatal lung disease

Clinical Science ◽

10.1042/cs0810439 ◽

1991 ◽

Vol 81 (3) ◽

pp. 439-446 ◽

Cited By ~ 31

Author(s):

F. J. Kelly ◽

G. I. Town ◽

G. J. Phillips ◽

S. T. Holgate ◽

W. R. Roche ◽

...

Keyword(s):

Animal Model ◽

Lung Injury ◽

Guinea Pig ◽

Bronchoalveolar Lavage ◽

Lung Disease ◽

Bronchoalveolar Lavage Fluid ◽

Small Animal ◽

Lavage Fluid ◽

Small Animal Model ◽

Neonatal Lung

1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig. 2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P < 0.05). 3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in preterm pups. 4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in preterm pups. 5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex. Lipase treatment reduced the activity of this fraction and generated a new 40 kDa fraction. 6. We conclude that the pre-term guinea-pig is more susceptible than the term animal to lung injury after O2 exposure and thus represents a appropriate small-animal model in which to investigate the pathogenesis of acute and chronic lung injury in the pre-term infant.

Download Full-text

Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

10.21236/ada424038 ◽

2004 ◽

Author(s):

Jefferey L. Burgess

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Predictive Value ◽

Lung Inflammation ◽

Time Course ◽

Smoke Inhalation

Download Full-text

Small Animal Model Mimics Poxvirus Infections

Microbe Magazine ◽

10.1128/microbe.2.608.1 ◽

2007 ◽

Vol 2 (12) ◽

pp. 608-608

Keyword(s):

Animal Model ◽

Small Animal ◽

Small Animal Model

Download Full-text

In vivo functional chronic imaging of a small animal model using optical-resolution photoacoustic microscopy

Medical Physics ◽

10.1118/1.3137572 ◽

2009 ◽

Vol 36 (6Part1) ◽

pp. 2320-2323 ◽

Cited By ~ 42

Author(s):

Song Hu ◽

Konstantin Maslov ◽

Lihong V. Wang

Keyword(s):

Animal Model ◽

Optical Resolution ◽

Small Animal ◽

Photoacoustic Microscopy ◽

Small Animal Model

Download Full-text

Rat-to-Chinese tree shrew heart transplantation is a novel small animal model to study non-Gal-mediated discordant xenograft humoral rejection

Xenotransplantation ◽

10.1111/xen.12211 ◽

2015 ◽

Vol 22 (6) ◽

pp. 468-475 ◽

Cited By ~ 2

Author(s):

WeiLi Chen ◽

Yuan Wu ◽

Akira Shimizu ◽

YinLong Lian ◽

Masayuki Tasaki ◽

...

Keyword(s):

Animal Model ◽

Heart Transplantation ◽

Tree Shrew ◽

Small Animal ◽

Humoral Rejection ◽

Small Animal Model

Download Full-text

Longitudinal Raman Spectroscopic Observation of Skin Biochemical Changes due to Chemotherapeutic Treatment for Breast Cancer in Small Animal Model

Journal of Spectroscopy ◽

10.1155/2017/3595078 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9

Author(s):

Myeongsu Seong ◽

NoSoung Myoung ◽

Songhyun Lee ◽

Hyeryun Jeong ◽

Sang-Youp Yim ◽

...

Keyword(s):

Breast Cancer ◽

Animal Model ◽

Raman Spectra ◽

Fiber Optic ◽

Animal Experiments ◽

Small Animal ◽

Fiber Optic Probe ◽

Small Animal Model ◽

Biochemical Compositions ◽

Optic Probe

The cancer field effect (CFE) has been highlighted as one of indirect indications for tissue variations that are insensitive to conventional diagnostic techniques. In this research, we had a hypothesis that chemotherapy for breast cancer would affect skin biochemical compositions that would be reflected by Raman spectral changes. We used a fiber-optic probe-based Raman spectroscopy to perform preliminary animal experiments to validate the hypothesis. Firstly, we verified the probing depth of the fiber-optic probe (~800 μm) using a simple intravenous fat emulsion-filled phantom having a silicon wafer at the bottom inside a cuvette. Then, we obtained Raman spectra during breast cancer treatment by chemotherapy from a small animal model in longitudinal manner. Our results showed that the treatment causes variations of biochemical compositions in the skin. For further validation, the Raman spectra will have to be collected from more populations and spectra will need to be compared with immunohistochemistry of the breast tissue.

Download Full-text

The differential expression of novel circular RNAs in an acute lung injury rat model caused by smoke inhalation

Journal of Physiology and Biochemistry ◽

10.1007/s13105-017-0598-5 ◽

2017 ◽

Vol 74 (1) ◽

pp. 25-33 ◽

Cited By ~ 7

Author(s):

Zhiqiang Ye ◽

Xuhui Liu ◽

Yuewu Yang ◽

Xianling Zhang ◽

Ting Yu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Differential Expression ◽

Rat Model ◽

Smoke Inhalation ◽

Circular Rnas

Download Full-text

Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection

Journal of Virology ◽

10.1128/jvi.00386-17 ◽

2017 ◽

Vol 91 (14) ◽

Cited By ~ 11

Author(s):

Liang Cui ◽

Jue Hou ◽

Jinling Fang ◽

Yie Hou Lee ◽

Vivian Vasconcelos Costa ◽

...

Keyword(s):

Fatty Acids ◽

Animal Model ◽

Bile Acid ◽

Dengue Virus ◽

Metabolic Pathways ◽

Dengue Infection ◽

Small Animal ◽

Humanized Mice ◽

Small Animal Model ◽

Serum Metabolomics

ABSTRACT Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend—most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly increased the challenges in the study of dengue pathogenesis and the development of therapeutics. Metabolomics provides global views of small-molecule metabolites and is a useful tool for finding metabolic pathways related to disease processes. Here, we conducted a serum metabolomics study on a model using humanized mice with dengue infection that had significant levels of human platelets, monocytes/macrophages, and hepatocytes. Forty-eight differential metabolites were identified, and the underlying perturbed metabolic pathways are quite similar to the pathways found to be altered in dengue patients in previous metabolomics studies, indicating that humanized mice could be a highly relevant small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.

Download Full-text