Abstract W P201: Angiopoietin-1 Mimetic Peptide Treatment of Stroke Regulates MicroRNA Expression and Promotes Neuroprotection in Type One Diabetic Rats
Bibliographic record
Abstract
Introduction: Angiopoietin-1 (Ang-1) mediates vascular remodeling. Diabetes decreases Ang1 and disrupts Ang1/Tie2 signaling, impairs vascular maturation and regulates immune response. MicroRNAs have been implicated in vascular diseases and inflammation. Vasculotide (VT) is an Ang1 mimetic peptide that promotes Tie2 activity. We hypothesize that treating type one diabetic rats (T1DM) with VT after stroke regulates miRNA expression decreases pro-inflammatory factors and thereby produces a neuroprotective effect. Methods: T1DM was induced in male Wistar rats with streptozotocin followed by 2h transient middle cerebral artery occlusion (MCAo). These rats were then treated with: 1) PBS control; 2) VT (3 ug/kg, ip injection) just prior to stroke and at 8h and 24h after MCAo. Functional tests were conducted 48h after MCAo. Afterwards, brain hemorrhage, BBB leakage, miRNA expression, RT-PCR, immunostaining and Western blot assays were done. Results: VT treatment did not decrease brain hemorrhage, but significantly decreased Evans Blue leakage (30.6±5.8 ng/mg vs. 17.9±2.0 ng/mg) lesion volume (35.1±3.5% vs 25.8±5.3%) and improved functional outcome after stroke when compared to control (p<0.05). To elucidate the mechanism, miRNA was measured. VT treatment significantly increased miR-451 (81.6 folds), miR-155 (2.4 fold), miR-98 (1.9 fold), and miR-126 (1.5 fold) expression, but decreased miR-200b (3.8 fold). Immunostaining showed that VT significantly decreased the number of apoptotic (45.5±3.7 vs 30.8±2.6) and cleaved-caspase-3 positive cells (45.2±3.5 vs 33.1±4.3), as well as monocyte chemotactic protein-1 (MCP1, 5.02±0.4% vs 1.8±0.2%) and tumor necrosis factor (TNF)-alpha (3.1±0.5% vs 1.5±0.2%). Western blot showed that VT significantly decreased receptor for advanced glycation end products (RAGE), MCP1 and TNFa (3-5 fold) in the ischemic border area compared to T1DM control. Conclusion: VT promotes neuroprotection after stroke in T1DM rats. Regulation of miRNA and neuroinflammatory factor expression and decreased BBB leakage may contribute to the VT induced neuroprotective effects observed after stroke in T1DM rats.
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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 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.005 | 0.001 |
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".