Abstract | BACKGROUND: MATERIALS AND METHODS: For in vivo experiments, healthy male Sprague-Dawley (SD) rats were applied to establish CA/ CPR model, and oxygen- glucose deprivation/reoxygenation (OGD/R)-stimulated neurons model was established in vitro. TWEAK short hairpin RNAs (shRNAs) were injected into the lateral ventricle of CA/ CPR rats or transfected into OGD/R cell culture to analyze the consequent alteration in neurological scores, behavioral tests, cell proliferation, cell apoptosis, and neuroinflammation through immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP- biotin nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA). RESULTS: There were high expressions of TWEAK and fibroblast growth factor-inducible 14 (Fn14) in the cerebral cortex of CA/ CPR rats and OGD/R-stimulated neuronal cells. TWEAK knockdown attenuated cell apoptosis, inflammation and showed better behavioral tests in CA/ CPR rats. Furthermore, TWEAK shRNAs obviously facilitated cell proliferation, suppressed apoptosis and inflammation after OGD/R injury. Western blotting results stated that TWEAK silencing promoted phosphorylated p38 (p-p38) and phosphorylated p65 (p-p65) expressions. CONCLUSIONS: TWEAK might be involved in the pathogenesis of CA/ CPR through inhibiting p38 MAPK/NF-κB pathway.
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Authors | Haifang Zhang, Ran Wang |
Journal | Discovery medicine
(Discov Med)
Vol. 35
Issue 177
Pg. 503-516
(08 2023)
ISSN: 1944-7930 [Electronic] United States |
PMID | 37553304
(Publication Type: Journal Article)
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Copyright | © 2023 The Author(s). Published by Discovery Medicine. |
Chemical References |
- NF-kappa B
- Tnfsf12 protein, rat
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Topics |
- Animals
- Male
- Rats
- Apoptosis
- Brain Injuries
(etiology, pathology)
- Heart Arrest
(complications, therapy)
- Inflammation
(metabolism)
- NF-kappa B
(metabolism)
- Rats, Sprague-Dawley
- Signal Transduction
(physiology)
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