AIF Overexpression Aggravates Oxidative Stress in Neonatal Male Mice After Hypoxia–Ischemia Injury
Bibliographic record
Abstract
There are sex differences in the severity, mechanisms, and outcomes of neonatal hypoxia-ischemia (HI) brain injury, and apoptosis-inducing factor (AIF) may play a critical role in this discrepancy. Based on previous findings that AIF overexpression aggravates neonatal HI brain injury, we further investigated potential sex differences in the severity and molecular mechanisms underlying the injury using mice that overexpress AIF from homozygous transgenes. We found that the male sex significantly aggravated AIF-driven brain damage, as indicated by the injury volume in the gray matter (2.25 times greater in males) and by the lost volume of subcortical white matter (1.71 greater in males) after HI. As compared to females, male mice exhibited more severe brain injury, correlating with reduced antioxidant capacities, more pronounced protein carbonylation and nitration, and increased neuronal cell death. Under physiological conditions (without HI), the doublecortin-positive area in the dentate gyrus of females was 1.15 times larger than in males, indicating that AIF upregulation effectively promoted neurogenesis in females in the long term. We also found that AIF stimulated carbohydrate metabolism in young males. Altogether, these findings corroborate earlier studies and further demonstrate that AIF is involved in oxidative stress, which contributes to the sex-specific differences observed in neonatal HI brain injury.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".