ArticleCNS neuroscience & therapeutics2025
Apelin-13 Attenuates Blood-Brain Barrier Dysfunction Following Intracerebral Hemorrhage via Targeting the Keap1/Nrf2 Signaling.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Plant-Derived Natural Compounds and Nrf2-Centered Redox Signaling in Intracerebral Hemorrhage: Evidence Grading, Mechanistic Boundaries, and Translational Challenges.Antioxidants (Basel, Switzerland) · 2026Review
- Effects of Different Doses of Ranolazine on SIRT1, APELA, and APL13 in a Rat MCAO Model.Current issues in molecular biology · 2026Article
- Alkannin Protects Against UVB-Induced Skin Photoaging by Targeting Keap1 to Activate the Nrf2/HO-1 Pathway.Molecules (Basel, Switzerland) · 2026Article
- Comments on "Jolkinolide B Mitigates Cerebral Ischemia-Reperfusion Injury by Promoting Microglial M1/M2 Polarization Through the JAK2/STAT3 Signaling Pathway".CNS neuroscience & therapeutics · 2026Article
- Computational pharmacovigilance of tranexamic acid: implications for intracerebral hemorrhage based on FAERS database and network toxicology.Frontiers in pharmacology · 2026Article
- Apelin-13 Attenuates Blood-Brain Barrier Dysfunction Following Intracerebral Hemorrhage via Targeting the Keap1/Nrf2 Signaling.CNS neuroscience & therapeutics · 2025Article
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Abstract
backgroundBlood-brain barrier (BBB) dysfunction serves as a critical driver of the secondary brain injury following intracerebral hemorrhage (ICH). Previous research has indicated that Apelin-13 demonstrates the potential to alleviate BBB dysfunction in various cerebrovascular disorders. However, the precise mechanisms through which Apelin-13 preserves BBB integrity remain elusive. This study investigated whether Apelin-13 exerted neuroprotective effects by targeting the Keap1/Nrf2 signaling.
methodsAn in vivo ICH model was established using collagenase. Neurological function, brain edema, tight junction protein levels, and Evans blue leakage were assessed. In vitro, bEnd.3 monolayers were induced by hemin to simulate ICH conditions. To assess the role of Apelin-13 in the Keap1/Nrf2 signaling, we employed specific shRNAs targeting Nrf2 and apelin receptor (APJ). The neuroprotective effects of Apelin-13 in hemin-stimulated bEnd.3 cells were assessed through transendothelial electrical resistance assay, western blotting, and immunofluorescence analysis.
resultsApelin-13 treatment significantly mitigated brain damage, reduced cerebral edema, and promoted neurological recovery in ICH mice. These effects were accompanied by a significant decrease in matrix metalloproteinase-9 expression and an increase in tight junction protein levels. Similar protective effects were observed in hemin-induced bEnd.3 cells, where Apelin-13 additionally promoted Nrf2 expression and suppressed Keap1 expression, suggesting the involvement of the Keap1/Nrf2 signaling. Critically, APJ silencing blocked the effects of Apelin-13 on the Keap1/Nrf2 pathway. Furthermore, Nrf2 knockdown eliminated the protective effects of Apelin-13, reversing its attenuation of apoptosis, preservation of tight junction integrity, and reduction of oxidative stress in hemin-stimulated bEnd.3 cells.
conclusionsIn conclusion, these findings demonstrate that through its engagement with APJ, Apelin-13 activates the endothelial Keap1/Nrf2 pathway to protect against ICH-induced BBB disruption and facilitate neurological recovery, highlighting its therapeutic promise for ICH.
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