Vasculotide restores the blood-brain barrier after focused ultrasound-induced permeability in a mouse model of Alzheimer's disease
Bibliographic record
Abstract
Focused ultrasound (FUS) is used to locally and transiently induce blood-brain barrier (BBB) permeability, allowing targeted drug delivery to the brain.The purpose of the current study is to evaluate the potential of Vasculotide to accelerate the recovery of the BBB following FUS disruption in the TgCRND8 mouse model of amyloidosis, characteristic of Alzheimer's disease (AD).Accelerating the restoration of the BBB post-FUS would represent an additional safety procedure, which could be beneficial for clinical applications.Methods: TgCRND8 mice and their non-transgenic littermates were treated with Vasculotide (250 ng, intraperitoneal) every 48 hours for 3 months.BBB permeability was induced using FUS, in presence of intravenously injected microbubbles, in TgCRND8 and non-transgenic mice, and confirmed at time 0 by MRI enhancement using the contrast agent gadolinium.BBB closure was assessed at 6, 12 and 20 hours by MRI.In a separate cohort of animals, BBB closure was assessed at 24-hours post-FUS using Evans blue injected intravenously and followed by histological evaluation.Results: Chronic Vasculotide administration significantly reduces the ultra-harmonic threshold required for FUS-induced BBB permeability in the TgCRND8 mice.In addition, Vasculotide treatment led to a faster restoration of the BBB following FUS in TgCRND8 mice.BBB closure after FUS is not significantly different between TgCRND8 and non-transgenic mice.BBB permeability was assessed by gadolinium up to 20-hours post-FUS, demonstrating 87% closure in Vasculotide treated TgCRND8 mice, as opposed to 52% in PBS treated TgCRND8 mice, 58% in PBS treated non-transgenic mice, and 74% in Vasculotide treated non-transgenic mice.In both TgCRND8 mice and non-transgenic littermates the BBB was impermeable to Evans blue dye at 24-hours post-FUS.Conclusion: Vasculotide reduces the pressure required for microbubble ultra-harmonic onset for FUS-induced BBB permeability and it accelerates BBB restoration in a mouse model of amyloidosis, suggesting its potential clinical utility to promote vascular health, plasticity and repair in AD.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".