Abstract 13235: Ischemic Preconditioning and Lazaroid (u-74389g) Administration Similarly Attenuate Ischemia-Reperfusion-Induced Spinal Cord Inflammatory and Apoptotic Responses by Targeting the S100-Receptor for Advanced Glycation End Product Pathway
Bibliographic record
Abstract
Introduction: Spinal cord injury and subsequent paraplegia represents a devastating complication of thoracoabdominal aortic surgery. Pro-inflammatory cytokine expression and spinal cord neuronal apoptosis have been implicated in inflammation and neurodegeneration respectively after ischemia. Hypothesis: We investigated the neuroprotective effects of the steroid antioxidant Lazaroid U-74389G versus conventional ischemic preconditioning (IPC) in a pig model of spinal cord ischemia-reperfusion injury by examining the expression of pro-inflammatory and pro-apoptotic S100 members and the receptor for advanced glycation end products (RAGE). Methods: Spinal cord ischemia was induced by thoracoabdominal aortic occlusion (TAO). A total of 27 pigs were randomized in four groups. Group I (n=5) sham operation, group II (n=7) TAO for 45min and received placebo, group III (n=8) received 3 doses of Lazaroid (3 mg/kg) 60min and 30min before and at 30min during TAO (duration 45min), and group IV (n=6) TAO for 20min followed by additional TAO for 45min and 80 minutes later. Neurologic evaluation was performed according to Tarlov score (0-4, 4=normal). The lumbar spinal cords were harvested at 7th postoperative day for the expression of inflammatory and apoptotic markers by real-time RT-PCR. Results: Group III and IV had better neurologic outcome postoperatively compared to group II where all animals developed paraplegia (Tarlov scores: 3.5 versus 3.6 versus 0.33, respectively, P<0.001). Group II showed marked pro-inflammatory responses as quantified by 2-4-fold increases in the mRNA of pro-inflammatory S100A6, S100A8 and high-mobility group box 1, and RAGE, compared to group I. Additionally, group II, exhibited apoptosis as quantified by a 40-60% decrease in the mRNA of anti-apoptotic BCL2 and BIRC2, and 2-3-fold increases in pro-apoptotic BAX mRNA and caspase 3 activity. Compared to group II, inflammatory and apoptotic responses were highly attenuated albeit to a similar degree in groups III and IV. Conclusions: In a large animal model very close to the clinical setting, we demonstrated that in addition to IPC, Lazaroid represents an alternative yet effective pharmacologic intervention in reducing spinal cord ischemia-reperfusion injury following TAO.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".