Adeno-associated Viral Delivery of Neurod1 to GFAP-expressing Cells of the Medial Prefrontal Cortex Post-stroke Reveals Ectopic Expression in Cortical Neurons
Bibliographic record
Abstract
Stroke is a leading cause of death and disability, often leaving survivors with motor and cognitive impairments. The delivery of neurogenic transcriptions factors (TFs) has been shown to induce astrocyte-to-neuron conversion in vitro and in vivo. Thus, we examined the potential of direct cellular reprogramming to treat cognitive impairments in a subacute model of stroke in the medial prefrontal cortex (mPFC) in Cre-conditional reporter mice. AAV5-GFAP::Cre or AAV5-GFAP::Neurod1Cre (pro-neural TF) was delivered to the perilesional cortex. We observed the unpredicted expression of Cre in neurons post-stroke in the mPFC of AAV5-GFAP::Cre injected brains, unlike motor cortex observations. These regional differences were consistent with the presence of GFAP mRNA in mPFC neurons. We observed cellular reprogramming 21 days following ectopic Neurod1 expression, which was sufficient to enhance cognitive recovery. Overall, this study demonstrated the impact of astrocyte-to-neuron reprogramming on cognitive behaviour following stroke and highlighted regional differences in this therapeutic approach.
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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 | 0.000 | 0.000 |
| 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".