Abstract WP293: Elucidating the Neuronal Basis of Diaschisis in Stroke Recovery
Bibliographic record
Abstract
Numerous studies have shown that focal ischemic stroke changes cortical activity patterns, metabolism and blood flow not only in peri-infarct regions, but also in remote regions connected to the ischemic core. This phenomenon known as “diaschesis”, was predicted over 100 years ago and is presumed to play an important role in dictating the extent of stroke recovery. Although regional brain imaging studies provide some support to this idea (with caveats), direct examination of the structure and function of neurons connected to neurons lost in the infarct core, has not been adequately addressed. One reason for our lack of a detailed understanding is the methodologies to trace connected neurons and track their function/activity patterns over weeks and months time after stroke, did not exist until recently. To address this issue, we injected adeno-associated virus (AAV) into the adult mouse primary forelimb somatosensory cortex (FLS1) 2-3 weeks before induction of photothrombotic stroke. These AAVs could either be transported in a retrograde fashion to label neural inputs to the FLS1 (retro pAAV.CAG.GFP), or conversely move in an anterograde, trans-synaptic manner (AAV.Syn.Cre) to label neurons downstream of FLS1 neurons, such as in motor cortex. In the latter case, we utilized a transgenic mouse that co-expressed a cre-recombinase dependent fluorescent reporter (tdTomato), as well as a genetically encoded calcium sensor (GCaMP6s) in neurons. These dual reporters (tdTomato and GCaMP6s) allowed us to examine changes in dendritic structure as well as functional activity patterns in downstream motor neurons. Our initial findings using confocal microscopy to assess dendritic structure, indicate subtle changes in spine density in neuronal inputs and outputs of the FLS1, within the first week after stroke. Repeated in vivo imaging of calcium transients in downstream motor cortex neurons in awake mice before and after FLS1 cortex stroke, suggested a long lasting disruption in neuronal and ensemble activity patterns. These preliminary findings provide direct evidence that neurons in remotely connected brain regions suffer long-lasting impairments after stroke, thereby providing another potential target or substrate for future therapeutics to consider.
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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 | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".