Apelin-13 attenuates microglia-mediated neuroinflammation following intracerebral hemorrhage via targeting JAK2/STAT3 signaling pathway
Bibliographic record
Abstract
BACKGROUND: Neuroinflammation is a critical contributor to secondary brain injury and subsequent neurological decline after intracerebral hemorrhage (ICH). Apelin-13, the most bioactive isoform of the endogenous G protein-coupled receptor (GPCR) ligand, exhibits protective roles in multiple neurological disorders. Nevertheless, its therapeutic effects and underlying mechanisms in neuroinflammation following ICH remain elusive. METHODS: In vivo, ICH was induced in mice with collagenase type VII, followed by intracerebroventricular injection of Apelin-13. In vitro, BV2 microglia were pretreated with Apelin-13 overnight, followed by lipopolysaccharide (LPS) stimulation. To investigate the mechanistic role of Apelin-13, we employed specific shRNA for APJ knockdown and the selective JAK2/STAT3 inhibitor WP1066 for pathway blockage. Western blotting and immunofluorescence assays were applied to assess JAK2/STAT3 signaling activation and pro-inflammatory mediator expression. RESULTS: Apelin-13 significantly decreased hematoma volume and mitigated neurological impairments in ICH mice. Correspondingly, both in vivo and in vitro studies confirmed its efficacy in attenuating microglia-mediated neuroinflammation. Mechanistically, Apelin-13 significantly suppressed JAK2/STAT3 signaling pathway in LPS-stimulated BV2 microglia. This suppression was reversed by APJ knockdown, verifying the necessity of the Apelin-13/APJ interaction. Furthermore, combining WP1066 with Apelin-13 significantly enhanced its anti-inflammatory effects, as evidenced by a more pronounced reduction in p-JAK2/p-STAT3 levels and pro-inflammatory cytokine secretion. Finally, the inhibition of the microglial JAK2/STAT3 pathway by Apelin-13 was also confirmed in the perihematomal brain tissues of ICH mice. CONCLUSIONS: Apelin-13 attenuated brain injury after ICH by suppressing microglia-mediated neuroinflammation through APJ receptor-dependent inhibition of the JAK2/STAT3 pathway.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".