Uric acid and ammonia play synergistic roles in the loss of blood-brain barrier integrity in the context of hepatic encephalopathy
Bibliographic record
Abstract
BACKGROUND: The blood-brain barrier (BBB) maintains brain homeostasis by regulating molecular entry. Its endothelial cells are joined by tight junction proteins and express few apical transporters. Hyperuricemia, known to impair tight junctions and endothelial function, may similarly affect the BBB. While ammonia freely diffuses across the BBB, its impact on endothelial integrity is unclear. This study investigates the combined effects of uric acid (UA) and ammonia on BBB function. METHODS: The BBB integrity in bile-duct ligated rats with hyperuricemia was investigated by evaluating permeability to UA, endothelial cell apoptosis and expression of tight junction proteins in the cerebral cortex. To mimic the conditions described in BDL rat, cultured primary rat brain microvascular endothelial cells (RBMEC), cells were exposed to UA (300 µmol/L) and ammonia (200 or 800 µmol/L) for 20 h prior to assessing the endothelial layer resistance, cell viability and expression of tight junction proteins. RESULTS: Both BDL rats and RBMEC cells exposed to UA and ammonia present with a significant loss of BBB integrity shown by an increased permeability to UA in rats and a decrease endothelial layer resistance in cells. Additionally, both in rats and RBMEC exposure to UA increases endothelial cell apoptosis and exposure to ammonia decreases the expression and integrity of tight junction proteins. CONCLUSIONS: The effects of uric acid on endothelial cell viability and of ammonia on tight junction integrity leads to a combined effect of both these molecules on the integrity of the BBB.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".