scholarly journals Using selective lung injury to improve murine models of spatially heterogeneous lung diseases

2018 ◽  
Author(s):  
Andrew J. Paris ◽  
Lei Guo ◽  
Ning Dai ◽  
Jeremy B. Katzen ◽  
Pryal N. Patel ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Lung Injury ◽  
Lung Diseases ◽  
Severe Injury ◽  
Regional Heterogeneity ◽  
Induce Lung Injury ◽  
Initial Injury ◽  
Diffuse Injury ◽  
Injury Models ◽  
Healthy Lung

AbstractMany lung diseases, such as acute respiratory distress syndrome (ARDS), display significant regional heterogeneity, with patches of severely injured tissue adjacent to apparently healthy tissue. Current mouse models that aim to mimic ARDS generally produce diffuse injuries that cannot reproducibly generate ARDS’s regional heterogeneity. This deficiency prevents the evaluation of how well therapeutic agents reach the most injured regions, and precludes many regenerative medicine studies, since it is not possible to know which apparently healing regions suffered severe injury initially. Finally, these diffuse injury models must be mild to allow for survival, as their diffuse nature does not allow for residual healthy lung to keep an animal alive long enough for many drug and regenerative medicine studies. To solve all of these deficiencies of current animal models, we have created a simple and reproducible technique to selectively induce lung injury in specific areas of the lung. Our technique, catheter-in-catheter selective lung injury (CICSLI), involves guiding an inner catheter to a particular area of the lung and delivering an injurious agent mixed with nanoparticles (fluorescently and/or radioactively labeled) that can be used to track the location and extent of where the initial injury was, days later. Further, we demonstrate that CICSLI can produce a more severe injury than diffuse models, yet has much higher survival since CICSLI intentionally leaves undamaged lung regions. Collectively, these attributes of CICSLI will allow better study of how drugs act within heterogeneous lung pathologies and how regeneration occurs in severely damaged lung tissue, thereby aiding the development of new therapies for ARDS and other lung diseases.

scholarly journals Ginsenoside Rh2 Ameliorates Lipopolysaccharide Induced Acute Lung Injury by Regulating the TLR4/ PI3K/Akt/mTOR, Raf-1/MEK/ERK and Keap1/Nrf2/HO-1 Signaling Pathways in Mice

2018 ◽  
Author(s):  
Yung-Hung Hsieh ◽  
Jeng-Shyan Deng ◽  
Chang Yuan-Shiun ◽  
Guan-Jhong Huang
Keyword(s):  
Lung Injury ◽  
Lung Diseases ◽  
Anterior Segment ◽  
Ginsenoside Rh2 ◽  
Lps Challenge ◽  
Induce Lung Injury ◽  
Anti Inflammatory ◽  
Antioxidant Effects ◽  
Inflammatory Effect

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

O2- and pneumonia-induced lung injury. I. Pathological and morphometric studies

1989 ◽  
Vol 67 (1) ◽  
pp. 346-356 ◽  
Author(s):  
J. J. Coalson ◽  
R. J. King ◽  
V. T. Winter ◽  
T. J. Prihoda ◽  
A. R. Anzueto ◽  
...  
Keyword(s):  
Intensive Care ◽  
Oleic Acid ◽  
Lung Injury ◽  
Lamellar Body ◽  
Study Groups ◽  
Alveolar Wall ◽  
Type I ◽  
Type Ii ◽  
Initial Injury ◽  
Injury Models

The physiological, morphological, and morphometric findings of several lung injury models in baboons have been compared in the following six study groups: 1) initial injury with oleic acid followed by ventilation with 100% O2, 2) ventilation with 100% O2, 3) ventilation with 80% O2, 4) ventilation with 80% O2 followed by inoculation of Pseudomonas aeruginosa, 5) ventilation with 40% O2, and 6) normal nonventilated room-air-breathing animals. The animals were maintained for 11 days in an intensive care unit. Light microscopically, animals ventilated with 40 and 80% O2 showed mild lung injury, consisting mostly of an increase in alveolar macrophages in peribronchiolar sites and focal alveolar wall widening. The 100% O2-oleic acid, 100% O2, and 80% O2-Pseudomonas-treated baboons showed mixed exudative-reparative diffuse alveolar lesions. Ultrastructurally, the type II cells of these three groups had significantly altered morphology with aberrations of lamellar body configurations. Morphometric findings showed increases in type II and interstitial cells and decreases in type I and endothelial cells in these injured animals. A striking finding was that the physiological, morphological, and morphometric changes of an 80% O2-Pseudomonas insult was as injurious as 100% O2. This synergistic effect of hyperoxia and infection very likely reflects the most frequent evolution of adult respiratory distress syndrome in patients in intensive care units.

Nanopharmaceutical-based regenerative medicine: Promising therapeutic strategy for spinal cord injury

2021 ◽  
Author(s):  
Chen Zhao ◽  
Zheng Xing ◽  
Chunchen Zhang ◽  
Yubo Fan ◽  
Haifeng Liu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Regenerative Medicine ◽  
Neurological Disorder ◽  
Therapeutic Strategy ◽  
Severe Injury ◽  
Cord Injury

Spinal cord injury (SCI) is a neurological disorder that can lead to loss of perceptive and athletic function due to the severe injury of nerve. Nowadays, evidences detailing the precise...

scholarly journals Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

2021 ◽  
Author(s):  
G. Amato ◽  
T. Saleh ◽  
G. Carpino ◽  
E. Gaudio ◽  
D. Alvaro ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Cell Therapy ◽  
Cell Delivery ◽  
Effective Strategies ◽  
Multiple Strategies ◽  
End Stage ◽  
Therapy Strategies ◽  
Injury Models ◽  
Experimental Liver

Abstract Purpose of Review To describe experimental liver injury models used in regenerative medicine, cell therapy strategies to repopulate damaged livers and the efficacy of liver bioengineering. Recent Findings Several animal models have been developed to study different liver conditions. Multiple strategies and modified protocols of cell delivery have been also reported. Furthermore, using bioengineered liver scaffolds has shown promising results that could help in generating a highly functional cell delivery system and/or a whole transplantable liver. Summary To optimize the most effective strategies for liver cell therapy, further studies are required to compare among the performed strategies in the literature and/or innovate a novel modifying technique to overcome the potential limitations. Coating of cells with polymers, decellularized scaffolds, or microbeads could be the most appropriate solution to improve cellular efficacy. Besides, overcoming the problems of liver bioengineering may offer a radical treatment for end-stage liver diseases.

scholarly journals Animal models of bronchopulmonary dysplasia. The term mouse models

2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Mouse Models ◽  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Invasive Mechanical Ventilation ◽  
Therapeutic Interventions ◽  
Contributing Factors ◽  
Short Term ◽  
Injury Models

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

scholarly journals An in Vitro Model of Blast Induce Lung Injury using Shock Tube

2019 ◽  
Vol 2 (2) ◽  
pp. 1-9
Author(s):  
Zhixin Liang ◽  
Zhaorui Zhang ◽  
Huaidong Li ◽  
Liang’an Chen
Keyword(s):  
Lung Injury ◽  
Shock Tube ◽  
In Vitro Model ◽  
Induce Lung Injury ◽  
Vitro Model

Cytoplasts and Mo1-deficient neutrophils pretreated with plasma and LPS induce lung injury

1989 ◽  
Vol 256 (3) ◽  
pp. H751-H759
Author(s):  
M. L. Wencel ◽  
M. L. Morganroth ◽  
S. O. Schoeneich ◽  
D. E. Gannon ◽  
J. Varani ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Parenchyma ◽  
Fixed Number ◽  
Receptor Expression ◽  
Human Neutrophils ◽  
Neutrophil Adhesion ◽  
Cell Monolayers ◽  
Induce Lung Injury ◽  
Surface Receptor ◽  
Normal Human

We hypothesized that neutrophil adhesion and lung injury could occur independent of the surface receptor glycoprotein, Mo1 (C3bi receptor). We investigated whether preincubation of human neutrophil-derived cytoplasts (cell fragments that lack nuclei and granules and have a fixed number of surface Mo1 receptors) with plasma and lipopolysaccharide (LPS) would augment the cytoplasts' ability to cause lung injury when activated. We also investigated whether preincubating normal human neutrophils treated with anti-Mo1 antibody with plasma and LPS would increase the neutrophils' ability to adhere and cause lung injury. Human neutrophils infused into isolated salt-perfused rat lungs subsequently stimulated with phorbol 12-myristate 13-acetate (PMA) resulted in lung injury as assessed by the accumulation of 125I-bovine serum albumin in the lung parenchyma. The infusion of cytoplasts resulted in significantly less injury. Cytoplasts preincubated in 20% human plasma and LPS caused an increase in lung injury. Similarly, neutrophils treated with plasma, LPS, and anti-Mo1 antibody or neutrophils congenitally deficient in the Mo1 surface receptor and treated with plasma and LPS augmented lung injury. Plasma and LPS preincubation also increased anti-Mo1 antibody-treated neutrophil adhesion to endothelial cell monolayers after activation by PMA. Thus, plasma and LPS increase adhesion and lung injury caused by neutrophils or neutrophil fragments that share defects in Mo1 receptor expression.

Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model

2008 ◽  
Vol 36 (12) ◽  
pp. 3205-3212 ◽  
Author(s):  
Fabienne Brégeon ◽  
Laurent Papazian ◽  
Stéphane Delpierre ◽  
Osamu Kajikawa ◽  
Marie-José Payan ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Lung Injury ◽  
Gastric Juice ◽  
Induce Lung Injury ◽  
Proinflammatory Activity

scholarly journals The Nitrated Fatty Acid 10-Nitro-oleate Diminishes Severity of LPS-Induced Acute Lung Injury in Mice

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Aravind T. Reddy ◽  
Sowmya P. Lakshmi ◽  
Raju C. Reddy
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Lung Diseases ◽  
Oxidant Stress ◽  
Pulmonary Delivery ◽  
Lung Edema ◽  
Potential Utility ◽  
Capillary Leakage ◽  
Nitrated Fatty Acid

Acute lung injury (ALI) is an inflammatory condition culminating in respiratory failure. There is currently no effective pharmacological treatment. Nitrated fatty acids (NFAs) have been shown to exert anti-inflammatory effects. We therefore hypothesized that delivery of NFAs directly to the site of inflammation would reduce the severity of ALI. Pulmonary delivery of 10-nitro-oleate following endotoxin-induced ALI in mice reduced markers of lung inflammation and injury, including capillary leakage, lung edema, infiltration of neutrophils into the lung, and oxidant stress, as well as plasma levels of proinflammatory cytokines. Nitro-oleate delivery likewise downregulated expression of proinflammatory genes by alveolar macrophages, key cells in regulation of lung inflammation. These effects may be accounted for by the observed increases in the activity of PPAR-γand the PPAR-γ-induced antioxidant transcription factor Nrf2, together with the decreased activity of NF-κB. Our results demonstrate that pulmonary delivery of NFAs reduces severity of acute lung injury and suggest potential utility of these molecules in other inflammatory lung diseases.

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