Metformin effects on brain development following cranial irradiation in a mouse model
Bibliographic record
Abstract
BACKGROUND: Cranial radiation therapy (CRT) is a mainstay of treatment for malignant pediatric brain tumors and high-risk leukemia. Although CRT improves survival, it has been shown to disrupt normal brain development and result in cognitive impairments in cancer survivors. Animal studies suggest that there is potential to promote brain recovery after injury using metformin. Our aim was to evaluate whether metformin can restore brain volume outcomes in a mouse model of CRT. METHODS: C57BL/6J mice were irradiated with a whole-brain radiation dose of 7 Gy during infancy. Two weeks of metformin treatment started either on the day of or 3 days after irradiation. In vivo magnetic resonance imaging was performed prior to irradiation and at 3 subsequent time points to evaluate the effects of radiation and metformin on brain development. RESULTS: Widespread volume loss in the irradiated brain appeared within 1 week of irradiation with limited subsequent recovery in volume outcomes. In many structures, metformin administration starting on the day of irradiation exacerbated radiation-induced injury, particularly in male mice. Metformin treatment starting 3 days after irradiation improved brain volume outcomes in subcortical regions, the olfactory bulbs, and structures of the brainstem and cerebellum. CONCLUSIONS: Our results show that metformin treatment has the potential to improve neuroanatomical outcomes after CRT. However, both timing of metformin administration and subject sex affect structure outcomes, and metformin may also be deleterious. Our results highlight important considerations in determining the potential benefits of metformin treatment after CRT and emphasize the need for caution in repurposing metformin in clinical studies.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".