Impact of a MTHFR-Deficiency on Focal Ischemic Damage to the Sensorimotor Cortex in Aged Mice
Bibliographic record
Abstract
Effective therapeutics in stroke are presently limited by a lack of translation from basic science to the clinic.Accumulation of excess plasma homocysteine is a risk factor for stroke.The B-vitamin, folate, helps to reduce plasma homocysteine among other important roles in the normal and diseased brain.Methylenetetrahydrofolate reductase (MTHFR) is the pivotal enzyme in folate metabolism that helps reduce homocysteine and could potentially modify stroke outcome.There is a highly prevalent polymorphism for Mthfr within the human population resulting in a MTHFR deficiency and elevated plasma homocysteine levels.The present study investigates the impact of a MTHFR deficiency on stroke outcome using a clinically relevant aged mouse model that mimics the MTHFR polymorphism in humans.Eighteen-month-old male C57BL/6N mice were subjected to photothrombosis delivered unilaterally to the sensorimotor cortex followed by assessment of motor function including the single pellet reaching task for up to 5 weeks, the ladder beam, the accelerated rotarod and the forepaw asymmetry task.Lesion volume and immunofluorescence of apoptotic, antioxidant and inflammatory activity were assessed.MTHFR deficient mice show significant impairments in skilled reaching for up to 5 weeks.After 5 weeks, caspase-3 expression was significantly elevated at the ischemic core of MTHFR deficient mice.No significant changes in motor function, lesion volume, antioxidant activity nor microglial cell activation were detected.Regardless of damage, MTHFR deficient mice showed elevated levels of plasma homocysteine.This study is the first to demonstrate in vivo exacerbation of stroke outcome in a MTHFR deficient animal model.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 | 0.001 |
| 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".