Abstract WP566: Vascular Regeneration Following Transient Hypertension by Perivascular Progenitor Cells and Abeta Clearance in a Transgenic Rat Model of Alzheimer’S Disease
Bibliographic record
Abstract
The interplay between hypertension and amyloidogensis is understudied and lacks of preclinical model that captures both pathologies. Our therapeutic approach is designed to target the patients who present cerebrovascular injury in combination with AD pathology. We combined induced transient hypertension (via Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) in a transgenic rat model of AD that recapitulates Aβ peptide deposition and tau hyperphosphorylation in the adulthood followed by cognitive decline and neuronal loss in later life. We administered human umbilical cord perivascular cells (HUCPVC) to elicit brain vascular repair and scyllo-inositol (SI) to clear amyloid. Treatment outcomes were measured by perfusion MRI, immunohistochemistry (amyloid, tau hyperphosphorylation, vascular markers), and immunoblotting. Four weeks after the cessation of L-NAME, a single HUCPVC treatment was administered, and final imaging session conducted four weeks thereafter. Blood-flow was measured during both rest and CO 2 challenges at: baseline, immediately post-L-NAME, and at endpoint. L-NAME administration induced moderate hypertension in both TgAD-F344 and non-TgAD rats, manifested by increased systolic pressure, elevated plasminogen activator inhibitor-1, decreased vessel density and hippocampal resting perfusion reduction. Hippocampal hypoperfusion in the non-TgAD animals returned to baseline 4-weeks after cessation of L-NAME, whereas in TgAD-F344 rats it persisted until endpoint and was not rescued by HUCPVC+SI. Hippocampal vascular responsivity to hypercapnia increased twice as much in TgAD-F344 when compared to non-TgAD-F344 following L-NAME administration; it did not return to baseline levels 4-weeks after cessation of L-NAME in the vehicle-administered TgAD-F344 rats, whereas HUCPVC and HUCPVC+SI rescued hippocampal cerebrovascular hyperreactivity to baseline levels of TgAD-F344 rats. Transient hypertension caused sustained cerebrovascular dysfunction when associated with Aβ plaques, revealing an interaction between transient hypertension and AD pathology. Combinatorial treatment with SI and HUCPVC may be necessary to address cerebrovascular disease with comorbid 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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".