Two-Photon Imaging of Stroke Onset<i>In Vivo</i>Reveals That NMDA-Receptor Independent Ischemic Depolarization Is the Major Cause of Rapid Reversible Damage to Dendrites and Spines
Bibliographic record
Abstract
We adapt a mouse global ischemia model to permit rapid induction of ischemia and reperfusion in conjunction with two-photon imaging to monitor the initial ionic, structural, and functional implications of brief interruptions of blood flow (6-8 min) in vivo. After only 2-3 min of global ischemia, a wide spread loss of mouse somatosensory cortex apical dendritic structure is initiated during the passage of a propagating wave (3.3 mm/min) of ischemic depolarization. Increases in intracellular calcium levels occurred during the wave of ischemic depolarization and were coincident with the loss of dendritic structure, but were not triggered by reperfusion. To assess the role of NMDA receptors, we locally applied the antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] at concentrations sufficient to fully block local NMDA agonist-evoked changes in intracellular calcium levels in vivo. Changes in dendritic structure and intracellular calcium levels were independent of NMDA receptor activation. Local application of the non-NMDA glutamate receptor antagonist CNQX also failed to block ischemic depolarization or rapid changes in dendrite structure. Within 3-5 min of reperfusion, damage ceased and restoration of synaptic structure occurred over 10-60 min. In contrast to a reperfusion promoting damage, over this time scale, the majority of spines and dendrites regained their original structure during reperfusion. Intrinsic optical signal imaging of sensory evoked maps indicated that reversible alteration in dendritic structure during reperfusion was accompanied by restored functional maps. Our results identify glutamate receptor-independent ischemic depolarization as the major ionic event associated with disruption of synaptic structure during the first few minutes of ischemia in vivo.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".