Publication related to work conducted on acute respiratory distress syndrome
The impact of time intervals on drug efficacy and phenotypic outcomes in acute respiratory distress syndrome (ARDS) in mice.
Acute Respiratory Distress Syndrome (ARDS) is a severe pulmonary condition resulting from various etiologies, with potentially fatal consequences requiring intensive care. This phenomenon can be modeled in preclinical settings, notably through lipopolysaccharide (LPS) instillation in mice. The induced phenotype closely recapitulates the human syndrome, encompassing pulmonary edema, leukocyte infiltration, acute inflammation, impaired lung function, and histological damage. However, experimental designs employing LPS instillations are highly diverse across the literature. This significantly complicates the interpretation of the induced phenotype's timeline for future study design and impedes the appropriate identification of the optimal temporal window for evaluating various endpoints. Consequently, defining the treatment window relative to disease onset also poses a significant challenge for addressing research questions or testing compound efficacy. In this context, the temporality of various endpoints typically measured in the model was assessed in normal and neutrophil-depleted male C57bl/6 mice using LPS induction, to determine the optimal window for appropriate endpoint evaluation with an optimal dynamic response range. Ventilation parameters were assessed by whole-body plethysmography, and neutrophil recruitment was evaluated in bronchoalveolar lavage fluids and directly in lung tissues. Myeloperoxidase imaging assessment, along with its activity in lung lysates and fluids, was compared, as were inflammatory cytokines and pulmonary extravasation via enzyme-linked immunosorbent assays. Furthermore, dexamethasone, the reference positive control in this model, was also administered at different time points before and after phenotype induction to evaluate how kinetics affected each parameter. Overall, our data demonstrate that each endpoint evaluated in this study exhibits unique kinetics and underscore the critical importance of timing between ARDS phenotype development and treatment administration and/or analysis. These findings also strongly suggest that analyses, both in vivo and post-mortem, should be conducted at multiple time points to accurately capture the dynamic phenotype of the LPS-induced ARDS model and its response to treatment.
Read the article (in English) here: https://www.nature.com/articles/s41598-024-71659-x
TransBioTech researchers associated with the publication: Sarah Paris-Robidas, Carole-Ann Huppé, Frédéric Couture
