Ibuprofen fails to prevent brain pathology in a model of neuropsychiatric lupus.
Bibliographic record
Abstract
OBJECTIVE: Neurologic and psychiatric manifestations are severe complications of systemic lupus erythematosus (SLE). As commonly seen in patients, spontaneous development of lupus-like disease in MRL-lpr mice is accompanied by brain atrophy and behavioral dysfunction. We examined inflammatory and ultrastructural aspects of central nervous system (CNS) involvement using a nonselective cyclooxygenase-2 (COX-2) inhibitor and measuring effects on behavior, microglial activation, and neuronal morphology. METHODS: Ibuprofen (IBU) was provided in a rodent chow (375 ppm) for animals 5-19 weeks of age. Exploration of a novel environment and performance in the forced swim test assessed effects on behavior. Immunohistochemistry, fluoro-Jade B (FJB) staining, and flow cytometry were employed in neuropathological analysis. Transmission electron microscopy was used to examine ultrastructural morphology of cortical, hippocampal, hypothalamic, nigral, and cerebellar cells. RESULTS: Chronic IBU treatment failed to normalize immune status, behavior, and brain mass in lupus-prone MRL-lpr mice. It also did not reduce density of CD3+ lymphocytes in the choroid plexus, or FJB+ neurons in the hypothalamus. Activated F4/80+ microglia increased with age, but IBU treatment was not effective in reducing their numbers. Although numerous dark cells were seen in functionally critical brain regions (e.g., paraventricular nucleus and subgranular zone), ultrastructural morphologies of classical apoptosis or necrosis were not detected. CONCLUSION: The COX-dependent pathway does not seem to be critical in the etiology of CNS disease in this model of neuropsychiatric lupus. Reduced brain mass, increased microglial activation, and condensation of cytoplasm point to a metabolic perturbation (e.g., excitotoxic damage) that compromises function and survival of central neurons during lupus-like disease.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".