Initiation site of experimentally-evoked spreading depolarizations influence tissue outcomes in a murine stroke model
Bibliographic record
Abstract
Spreading depolarization waves (SDs) are implicated in secondary expansion of brain injuries and are the target for initial clinical intervention trials. However, the assumption that SD directly causes neuronal injury has been challenged by recent findings with experimentally-induced SD in stroke models. The current study addressed this controversy by examining whether stroke consequences are confounded by the precise location of experimental SD initiation. Focal ischemic lesions were generated by transient distal middle cerebral artery occlusion in male mice. Clusters of SDs (6 at 10-min intervals) were induced by either focal KCl application or optogenetic stimulation during occlusion. SDs were initiated either in regions close to the infarct core (penumbral-SD; <50% perfusion) or in less compromised tissue in the same hemisphere (remote- SD; >70% perfusion). Despite the fact that all SDs fully invaded stroke expansion areas, the location of experimental SD induction had significant effects on stroke outcomes measured 48 hours after reperfusion. Penumbral-SDs resulted in larger infarct expansion than seen in control stroke mice lacking experimentally-imposed SD. Conversely, remote-SDs led to significantly smaller infarcts than stroke alone. Laser speckle contrast imaging of blood flow in injury expansion areas showed enhanced hypoperfusion responses after penumbral-SDs and larger hyperemic responses after remote-SDs, suggesting that differential vascular responses could contribute to stroke outcomes. Overall, this study helps to reconcile different prior reports by showing that experimentally-induced SDs can either exacerbate or reduce stroke-induced injury depending on the SD initiation site and further strengthens evidence for injurious roles of SDs initiating in vulnerable brain tissue.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".