Effects of a PDGFR-a Antagonist Imatinib on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia in Younger and Older Rats
Bibliographic record
Abstract
Background: One of the pathways involving blood-brain barrier (BBB) disruption in focal ischemia can act through the platelet derived growth factor a receptor (PDGFR- a ) system including PDGF-CC and tissue plasminogen activator (tPA). This study was performed to compare the effects of imatinib, a PDGFR- a antagonist, on blood-brain barrier (BBB) permeability in younger and older rats in focal cerebral ischemia and to determine whether the protein levels of PDGFR- a vary with age. Methods: Three month old (Younger) and 24 month old (Older) male Fischer 344 rats were used. One hour before middle cerebral artery (MCA) occlusion, rats were treated by gavage with normal saline (control) or imatinib mesylate 200 mg/kg. At one and a half hours after MCA occlusion, BBB permeability was determined by measuring the transfer coefficient (K i ) of 14 C- a -aminoisobutyric acid and volume of dextran distribution. Western blot analysis of PDGFR- a was performed on additional rats. Results: With MCA occlusion, the K i of the ischemic cortex (IC) significantly increased in both age groups. The K i of the IC of the older control rats was significantly lower ( - 57%) than that of the younger control rats. In the younger rats, imatinib significantly decreased the K i of the IC ( - 48%). In the older rats, however, imatinib failed to decrease the K i . The difference in volume of dextran distribution between the IC and the contralateral cortex was significant only in the younger control rats and became insignificant with imatinib. Imatinib did not affect the volume of dextran distribution in the older rats. Neither aging nor imatinib affected BBB permeability in non-ischemic brain regions. The ratio of density of PDGFR- a normalized for tubulin level was similar between the younger and older rats (younger: 0.85 ± 0.48 vs older: 0.93 ± 0.58). Conclusion: Imatinib decreased BBB disruption caused by focal cerebral ischemia in the younger rats but failed to decrease it in the older rats in spite of similar protein level of PDGFR- a . doi: http://dx.doi.org/10.4021/jnr118w
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| 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) | 0.000 | 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 teacher head, 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".