Mechanisms of neuroprotection against ischemic insult by stress‐inducible phosphoprotein‐1/prion protein complex
Bibliographic record
Abstract
Abstract Stress‐inducible phosphoprotein 1 ( STI 1) acts as a neuroprotective factor in the ischemic brain and its levels are increased following ischemia. Previous work has suggested that some of these STI 1 actions in a stroke model depend on the recruitment of bone marrow‐derived stem cells to improve outcomes after ischemic insult. However, STI 1 can directly increase neuroprotective signaling in neurons by engaging with the cellular prion protein (Pr P C ) and activating α7 nicotinic acetylcholine receptors (α7n AC hR). Given that α7n AC hR activation has also been involved in neuroprotection in stroke, it is possible that STI 1 can have direct actions on neurons to prevent deleterious consequences of ischemic insults. Here, we tested this hypothesis by exposing primary neuronal cultures to 1‐h oxygen‐glucose deprivation ( OGD ) and reperfusion and assessing signaling pathways activated by STI 1/Pr P C . Our results demonstrated that STI 1 treatment significantly decreased apoptosis and cell death in mouse neurons submitted to OGD in a manner that was dependent on Pr P C and α7n AC hR, but also on the activin A receptor 1 ( ALK 2), which has emerged as a signaling partner of STI 1. Interestingly, pharmacological inhibition of the ALK 2 receptor prevented neuroprotection by STI 1, while activation of ALK 2 receptors by bone morphogenetic protein 4 ( BMP 4) either before or after OGD was effective in decreasing neuronal death induced by ischemia. We conclude that Pr P C / STI 1 engagement and its subsequent downstream signaling cascades involving α7n AC hR as well as the ALK 2 receptor may be activated in neurons by increased levels of STI 1. This signaling pathway protects neurons from ischemic insults. image
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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 | 0.000 | 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) | 0.001 | 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".