ArticleCNS neuroscience & therapeutics2025
Metrnl/C-KIT Axis Attenuates Early Brain Injury Following Subarachnoid Hemorrhage by Inhibiting Neuronal Ferroptosis.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Evaluation of serum irisin and meteorin-like (METRNL) levels in people with drug-resistant and drug-responsive temporal lobe epilepsy.Epileptic disorders : international epilepsy journal with videotape · 2026Article
- Sestrin2 Mitigates Neuronal Ferroptosis Following Subarachnoid Hemorrhage via Orchestration of the AMPK/PGC1α/Nrf2 Signaling Axis.CNS neuroscience & therapeutics · 2026Article
- The Mechanism of Ferroptosis and Blood-Brain Barrier Damage in Cerebrovascular Diseases.Biomedicines · 2026Review
- Ferroptosis-Driven Neuronal Damage Exacerbation in Diabetic Stroke: Implications of SLC7A11 Inhibition.CNS neuroscience & therapeutics · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
background and purposeFerroptosis is a distinct form of cell death characterized by iron-dependent lipid peroxidation and plays a crucial role in the early brain injury (EBI) following subarachnoid hemorrhage (SAH). As a newly discovered endogenous ligand for the C-KIT receptor tyrosine kinase, meteorin-like protein (Metrnl) exerts regulatory functions in oxidative stress and protects against various diseases. However, the specific role of the Metrnl/C-KIT axis in neuronal ferroptosis during EBI following SAH remains to be elucidated.
methodsSprague Dawley rats were used to establish the SAH model through endovascular perforation. r-Metrnl was administered intranasally 1 h after SAH. Metrnl shRNA, C-KIT inhibitor ISCK03, AMPK inhibitor dorsomorphin, and Nrf2 inhibitor ML385 were administered intracerebroventricularly or intraperitoneally before r-Metrnl treatment to explore the underlying mechanisms. Neurobehavioral assessments, immunofluorescence, western blot, ELISA, Fluoro-Jade C staining, transmission electron microscopy, and Nissl staining were conducted to evaluate the effects. Additionally, primary neuron culture with hemoglobin (Hb) stimulation was used for in vitro studies.
resultsPhosphorylated C-KIT and endogenous Metrnl levels were upregulated after SAH. Knockdown of Metrnl aggravated neurobehavioral deficits and neuronal ferroptosis, whereas r-Metrnl treatment showed a protective effect. Mechanistically, r-Metrnl significantly increased the protein levels of SLC7A11, GPX4, FTH, FSP1, and GSH, whereas it decreased the levels of ACSL4, 4HNE, and MDA in the ipsilateral hemisphere 24 h after SAH. Also, r-Metrnl reduced mitochondrial shrinkage, increased mitochondrial crista, and decreased membrane density. However, the beneficial effects of r-Metrnl were partially reversed by ISCK03, dorsomorphin, or ML385 treatment both in vivo and in vitro.
conclusionsOur study demonstrated that r-Metrnl reduced neuronal ferroptosis and improved neurological outcomes after SAH by modulating the C-KIT/AMPK/Nrf2 signaling pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.