Abstract 2259: Age-related Increases In Microvascular Phosphodiesterase 4d Expression And Perimicrovascular Space Following Transient Global Ischemia In Rats
Bibliographic record
Abstract
Background and purpose. While a majority of clinical genomic studies indicate that the gene encoding phosphodiesterase 4D (PDE4D) increases risk of cerebral ischemia, the role of PDE4D in the actual pathogenic mechanisms of ischemia remains unclear. The present study attempts to define a role for PDE4D in the acute phase of cerebral ischemia by monitoring changes in microvascular PDE4D expression and changes in the inside bore of the microvasculature in young and aged rats. Methods. Male F344 rats aged 4- and 24-months were subjected to sham surgery (n=4/group): young control (YC) and aged control (AC) groups or transient global ischemia: young ischemia (YI, n=7) and aged ischemia (AI, n=8) groups. Histological assessments and measurements of PDE4D immunoreactivity in the hippocampus were performed 8 days following ischemia. Results. Perivascular tissue density (defined by an index of the intensity of weak positive per square micron) was significantly lower in the AC group than in the YC group (p<0.05, Fig. 1 E). Transient global ischemia elicited a significant decrease in tissue density in the perimicrovascular space in both young and aged animals as compared to controls ( Fig. 1 E). In addition, internal bore circumference and cross-sectional area increased dramatically as a result of ischemia ( Fig. 1 F). Ischemia also caused a severe loss of hippocampal CA1 neurons ( Fig. 2 A,B,C) in association with significant increases in PDE4D immunoreactivities ( Fig. 2 D-F). Interestingly, hippocampal neuron loss following ischemia paralleled PDE4D expression in microvessels: cell loss was accompanied by much higher levels of perivascular PDE4D expression with this effect being greater in the younger animals. In conclusion, decreases in perivascular tissue density and enlargements in microvascular bore likely indicate an increase in brain-blood barrier (BBB) permeability following the onset of ischemia. This is associated with an increased expression of PDE4D. Increased PDE4D expression following cerebral ischemia may play a role in changing BBB permeability and, thus, secondarily affect ischemic outcome.
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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 | 0.000 |
| 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) | 0.003 | 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".