Comparative Evaluation of LPS Administration Routes for Inducing Acute Lung Injury in Murine Models: Efficacy, Consistency and Technical Considerations
Bibliographic record
Abstract
ContextPreclinical lipopolysaccharide (LPS) acute lung injury (ALI) models are commonly used to study acute respiratory distress syndrome. Differences in LPS delivery methods may impact lung injury severity and reproducibility. Hypothesis We hypothesized that the severity and variability of ALI outcomes in mice would differ depending on the route of LPS administration. Methods and ModelsMale and female C57BL/6 mice were administered LPS (2.25 mg/kg) via four routes: 1) intratracheal intubation; 2) intranasal; 3) surgical trans-tracheal by either needle puncture or; 4) by catheter. ALI severity and variability were assessed at 72 hours post-LPS via histological scoring, bronchoalveolar lavage fluid (BALF) analysis (total protein, cell counts, IL-6). The relative distribution of Evans Blue dye was also assessed for each model (lungs vs. stomach).ResultsDistinct lung injury patterns were observed between the four routes. The trans-tracheal catheter route demonstrated significantly greater lung injury scores than the intratracheal intubation and intranasal routes. Both trans-tracheal routes led to greater alveolar neutrophil counts, increased proteinaceous debris, fewer hyaline membranes, and lower variability than non-surgical routes. The trans-tracheal catheter route produced higher BALF total cell counts and IL-6 levels than intratracheal intubation. Trans-tracheal routes also resulted in more localized Evans Blue dye distribution in the lungs. Male mice exhibited more severe lung injury scores and higher BALF protein concentrations than females.Interpretation and ConclusionsThis study demonstrates that LPS route choice impacts injury severity, phenotype, and variability. Both surgical trans-tracheal routes of LPS administration produced the most robust and least variable ALI phenotype, however they are also associated with increased procedural complexity. Our results will allow researchers to tailor their model choice to align with their specific study objectives.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".