The Role of One-Carbon Metabolism After Ischemic Stroke in an Aged Mouse Model
Bibliographic record
Abstract
Nutrition is a modifiable risk factor for stroke, which is one of the leading causes of death and disability world-wide. In humans deficiencies in one-carbon metabolism, including the methyltetrahydrofolate reductase (MTHFR) polymorphism, have been linked to increased risk of stroke. The Mthfr+/− mice mouse model mimics the phenotype of the MTHFR677C – >T polymorphism. In our work using in vitro and in vivo models of ischemic stroke we have observed decreased recovery after stroke through reduced neuronal and astrocyte viability and increased apoptosis in MTHFR-deficient mice. In addition, we have previously shown dietary supplementation of one-carbon metabolites increases neuroplasticity and reduced oxidative stress after ischemic stroke. Using the MTHFR-deficient mouse model, the aim of this study was to investigate the impact of dietary supplementation with one-carbon metabolites on stroke outcome. Male Mthfr+/− and wildtype littermate control mice were aged to 1.5-year-old and were placed on control diet (CD) 4-weeks prior to sensorimotor cortex damage using photothrombosis (PT), a model for ischemic stroke. Post-operatively, one group of Mthfr+/− and wildtype littermate mice were fed a supplemented diet (SD) containing 5-methylTHF, vitamin B12, and choline. Four weeks after PT damage and SD motor function was assessed and brain tissue was processed to assess lesion volume and investigate biochemical and molecular changes. Mthfr+/− mice fed a SD after PT did not have an impaired neuroscore compared to CD Mthfr+/− mice. When compared to CD, SD Mthfr+/− mice were able to stay on the accelerating rotarod longer and travelled further, they also used their impaired forepaw more. Total homocysteine levels in plasma and lesion volume were reduced in SD Mthfr+/+ and Mthfr+/− mice. In the brain, within the damage site, there were reduced levels of apoptotic cell death and an increased neuroprotective cellular response in SD treated Mthfr+/− mice. This study reveals a critical role for one-carbon supplementation in supporting improvement of function after ischemic stroke. Our data suggests that in stroke affected patients, nutritional supplementation maybe an important component to post-operative care, in addition to pharmacological and rehabilitation therapies. NSERC.
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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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".