Immune modulatory and vascular protective effects of Ibudilast in post-stroke inflammation
Bibliographic record
Abstract
Ischemic stroke induces sustained microvascular dysfunction and inflammation, contributing to futile recanalization and poor tissue recovery despite successful large-vessel reopening. Neutrophil adhesion and capillary stalling are key drivers of this microvascular failure. While Ibudilast, a small-molecule phosphodiesterase (PDE3/4) inhibitor with vasodilatory and anti-inflammatory properties, has shown promise in modulating neuroinflammation, its impact on post-stroke microvascular flow and neutrophil-mediated obstruction remains poorly understood. In this study, we investigated the effects of Ibudilast on cerebral perfusion, neutrophil dynamics, and infarct size following transient middle cerebral artery occlusion (MCAO) in young (4–6 months) and aged (18–20 months) male and female C57BL/6 mice, a design intended to reflect clinically relevant variability in stroke outcomes. Ibudilast (30 mg/kg, intraperitoneally) was administered at 30 min and 6 h post-occlusion, and in vivo imaging was performed at 3hPR and 24hPR to assess hemodynamic parameters and neutrophil behavior. Treatment preserved vessel diameter, maintained flow velocity, restored red blood cell flux, and enhanced perfusion in both surface and capillary compartments, with improvements most pronounced in young and female cohorts. Neutrophil adhesion and capillary stalling were reduced. In vehicle-treated animals, neutrophil stalls correlated strongly with impaired vascular flow, whereas this relationship was absent in the treated group. These microvascular improvements were accompanied by a significant reduction in infarct volume (>50 %) at 24hPR compared to vehicle-treated controls. Together, these findings highlight Ibudilast’s therapeutic potential for preserving microvascular integrity and guiding adjunctive interventions to mitigate futile recanalization in acute ischemic stroke. • Ibudilast confers multimodal neurovascular protection in acute ischemic stroke. • Treatment preserves flow dynamics in pial vessels and perfusion in capillary networks. • Ibudilast suppresses neutrophil accumulation and mitigates vascular damage. • Structural and functional vascular improvements are consistent across age and sex groups. • Ibudilast, a phosphodiesterase inhibitor, reduces infarct volume and supports translational potential in stroke therapy.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".