Abnormal neurovascular coupling induces glymphatic dysfunction in a mouse model of familial hemiplegic migraine type 2
Bibliographic record
Abstract
Migraine is a prevalent primary headache disorder that significantly impairs daily life. Recent imaging studies have suggested that chronic migraine may be associated with changes in the function of the glymphatic system. Here, we describe altered cortical physiology in a genetic mouse model of familial hemiplegic migraine type 2 (FHM2), with reduced expression of astrocytic Na+/K+-ATPases. We used cerebrospinal fluid (CSF) fluorescence tracing to demonstrate that impairment of the inflow and outflow functions of the glymphatic system was observed in FHM2 mice. Using two-photon recording, we observed exaggerated neurovascular coupling in the barrel cortex of FHM2 mice. This abnormal neurovascular coupling resulted in a decrease in AQP4 expression within the perivascular astrocyte endfoot. This alteration may be a significant mechanism contributing to impairment of the glymphatic system in FHM2 mice. In vitro, primary astrocyte cultures were established and it was found that astrocytes derived from FHM2 exhibited impaired K+ transport function, which may be associated with exaggerated neurovascular coupling. Overall, our study reveals that the glymphatic system is significantly impaired in FHM2 mice, with abnormal neurovascular coupling playing a key role in decreased AQP4 expression in astrocytes, this providing a new ways of approaching to migraine pathophysiology.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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 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".