Comprehensive Assessment of Drug Kinetics, Neurotoxicity, and Safety of Sirolimus-Eluting Intracranial Stents in Canine Basilar Artery
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVES: Sirolimus-eluting stents (SESs) have shown promise in treating intracranial atherosclerosis but concerns about potential neurotoxicity due to prolonged drug release exist. The aim of this study was to comprehensively assess the safety of SES, with a focus on neurotoxicity. METHODS: Stents (1.50 × 7 or 12 mm) were implanted into the basilar arteries of 154 Labrador Retrievers (weighing >25 kg and aged older than 1 year) divided into 4 groups: bare-metal stent, polymer-coated stent, standard-dose SES (sirolimus dose: 71 μg), and high-dose SES group (sirolimus dose: 284 μg). Pharmacokinetic analysis was conducted using liquid chromatography-mass spectrometry on blood and tissue samples, and analysis of brain tissue was performed with 5 different special stains and immunohistochemistry protocols to assess axonal degeneration, vacuolization, astrocyte proliferation, microglial activation, or widespread neurodegeneration. RESULTS: In the standard-dose SES group, the stent released 10.56% of the drug on day 1 and 95.41% on day 28 postimplantation. In the high-dose SES group, corresponding figures were 40.20% on day 1 and 98.08% on day 28. Systemic drug concentration consistently remained below 1.5 ng/mL throughout the study. Arterial tissue concentration reached its peak at day 28 days in the standard-dose group and at 7 days in the high-dose group. Importantly, the brain and related tissue concentrations remained below 0.4 µg/g in both standard-dose and high-dose SES groups, peaking on day 21 in the standard-dose group and day 1 in the high-dose group. The detailed 180-day safety assessment revealed no adverse effects on the brain, even at high sirolimus doses in the SES group. CONCLUSION: This study provides robust evidence supporting the long-term pharmacokinetic safety of SESs in the context of intracranial interventions for high-grade intracranial atherosclerosis. The results adequately alleviate concerns related to neurotoxicity and substantiate the feasibility of using these stents as a therapeutic choice in neurosurgery.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".