Arachidonic acid increases permeability of HBMEC monolayers via increased production of prostaglandin E2
Bibliographic record
Abstract
The blood‐brain barrier, formed by microvessel endothelial cells, is the restrictive barrier between the brain parenchyma and the circulating blood. Arachidonic acid (AA) is a conditionally essential polyunsaturated fatty acid [20:4(n‐6)] and a major constituent of brain lipids. In this study transport of AA in confluent monolayers of human brain microvessel endothelial cells (HBMEC) was examined. Addition of [3H]AA to the apical compartment of HBMEC confluent monolayers cultured on Transwell® inserts resulted in rapid incorporation of [3H]AA into the basolateral medium. Knock down of FATP‐1 or CD36 did not alter [3H]AA movement into the basolateral medium and this was due to a rapid generation of prostaglandin E2 (PGE2), an eicosanoid known to facilitate opening of the blood‐brain barrier. Disruption of HBMEC monolayers following AA exposure was confirmed by an increased movement of fluorescein‐labeled dextran from the apical to basolateral medium. HBMECs expressed PGE2 synthase, cyclooxygenase‐1 and ‐2, PGE2 receptors, tight junction proteins and prostaglandin transporters. Specific cyclooxygenase‐2 inhibitors attenuated the AA‐mediated increase in membrane permeability. The results indicate that AA increases the permeability of HBMEC monolayers via increased production of PGE2. [Funded by NSERC Canada; GMH is a Canada Research Chair in Molecular Cardiolipin Metabolism]
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".