Effects of Moderate Hypothermia on IL-1β–Induced Leukocyte Rolling and Adhesion in Pial Microcirculation of Mice and on Proinflammatory Gene Expression in Human Cerebral Endothelial Cells
Why this work is in the frame
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Bibliographic record
Abstract
SUMMARY: Although the neuroprotective effects of hypothermia have been known for a long time, the molecular correlates of this neuroprotection are poorly understood. In this study, the authors investigated how hypothermia affects inflammatory responses in the brain elicited by systemic injection of IL-1 beta. Leukocyte rolling and adhesion were quantified in pial venules (20 to 50 microm) of C57/Bl6 mice 4 hours after intraperitoneal injection of IL-1 beta (5 microg/kg) using an open cranial window and intravital microscopy. Animals were subjected to moderate hypothermia (32 degrees C) or normothermia (37 degrees C) for 1 or 4 hours after IL-1 beta injection. Significant increases in leukocyte rolling and adhesion were observed in IL-1 beta-injected animals as compared with sham controls. Whereas 1-hour hypothermia did not affect IL-1 beta-induced leukocyte rolling and adhesion, 4-hour hypothermia caused a reduction in both rolling and adhesion. Molecular mechanisms of hypothermic effects were investigated in cultured human cerebral endothelial cells exposed to IL-1 beta (50 U/mL) for 4 hours at 37 degrees C or 32 degrees C followed by 18 hours at 37 degrees C. Human cerebral endothelial cells exposed to IL-1 beta at 32 degrees C showed attenuated NF-kappa B activation determined by the Luciferase yellow reporter gene assay and reduced expression of IL-8 and IL-1 beta measured by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Intracellular adhesion molecule-1 was induced to similar levels (threefold over control) at both temperatures. The expression of CD18 on neutrophils in vitro was not affected by either IL-1 beta or hypothermia. These findings suggest that mechanisms by which hypothermia reduces leukocyte rolling and adhesion include suppression of inflammatory gene transcription in brain endothelial cells.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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) | 0.000 | 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 it