Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer’s disease rats
Bibliographic record
Abstract
Hypertension, including transient events, is a major risk factor for developing late-onset dementia and Alzheimer's disease (AD). Anti-hypertensive drugs facilitate restoration of normotension without amelioration of increased dementia risk suggesting that transient hypertensive insults cause irreversible damage. This study characterized the contribution of transient hypertension to sustained brain damage as a function of normal aging and AD. To model transient hypertension, we treated F344TgAD and non-transgenic littermate rats with L-NG-Nitroarginine methyl ester (L-NAME) for one month, ceased treatment and allowed for a month of normotensive recovery. We then examined the changes in the structure and function of the cerebrovasculature, integrity of white matter, and progression of AD pathology. As independent factors, both transient hypertension and AD compromised structural and functional integrity across the vascular bed, while combined effects of hypertension and AD yielded the largest deficits. Combined effects of transient hypertension and AD genotype resulted in loss of cortical myelin particularly in the cingulate cortex which is crucial for cognitive function. Increased cerebral amyloid angiopathy, a prominent pathology of AD, was detected after transient hypertension as were up- and down-regulation of proteins associated with cerebrovascular remodeling - osteopontin, ROCK1 and ROCK2, in F344TgAD rats even 30 days after restoration of normotension. In conclusion, transient hypertension caused permanent cerebrovasculature and brain parenchymal damage in both normal aging and AD. Our results corroborate human studies that have found close correlation between transient hypertension in midlife and white matter lesions later in life outlining vascular pathologies as pathological links to increased risk of dementia.
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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) | 0.000 | 0.000 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".