Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
Bibliographic record
Abstract
Unlabelled Box •von Willebrand Factor (VWF) and ADAMTS13 may affect early injury after subarachnoid hemorrhage (SAH). •Early brain injury was assessed in VWF −/− , ADAMTS13 −/− and recombinant (r) ADAMTS13 treated mice. •VWF −/− and rADAMTS13 treated mice had less brain injury than ADAMTS13 −/− and wild‐type mice. •Early administration of rADAMTS13 may improve outcome after SAH by reducing early brain injury. Baxalta US Inc. Brain Aneurysm Foundation Canadian Institutes of Health Research Ontario Genomics Summary: Background Early brain injury is an important determinant of poor functional outcome and case fatality after aneurysmal subarachnoid hemorrhage (SAH), and is associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated whether von Willebrand factor (VWF) is involved in the pathogenesis of early brain injury, and whether ultra‐early treatment with recombinant ADAMTS‐13 (rADAMTS‐13) reduces early brain injury after experimental SAH. Methods Experimental SAH in mice was induced by prechiasmatic injection of non‐anticoagulated blood from a littermate. The following experimental SAH groups were investigated: C57BL/6J control ( n = 21), VWF −/− ( n = 25), ADAMTS‐13 −/− ( n = 23), and C57BL/6J treated with rADAMTS‐13 ( n = 26). Mice were killed at 2 h after SAH. Primary outcome measures were microglial activation (IBA‐1 surface area) and neuronal injury (number of cleaved caspase‐3‐positive neurons). Results As compared with controls, microglial activation was decreased in VWF −/− mice (mean difference of − 20.0%, 95% confidence interval [CI] − 4.0% to − 38.6%), increased in ADAMTS‐13 −/− mice (mean difference of + 34.0%, 95% CI 16.2–51.7%), and decreased in rADAMTS‐13‐treated mice (mean difference of − 22.1%, 95% CI − 3.4% to − 39.1%). As compared with controls (185 neurons, interquartile range [IQR] 133–353), neuronal injury in the cerebral cortex was decreased in VWF −/− mice (63 neurons, IQR 25–78), not changed in ADAMTS‐13 −/− mice (53 neurons, IQR 26–221), and reduced in rADAMTS‐13‐treated mice (45 neurons, IQR 9–115). Conclusions Our findings suggest that VWF is involved in the pathogenesis of early brain injury, and support the further study of rADAMTS‐13 as a treatment option for early brain injury after SAH.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".