ArticleBrain and behavior2025
Nicorandil Ameliorates Depression-Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus.
Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review.International journal of molecular sciences · 2025Pooled it
- Ferroptosis in major depressive disorder: Molecular mechanisms, cellular vulnerability, and therapeutic opportunities.Biochemistry and biophysics reports · 2026Review
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- Nicorandil ameliorates neuropathic and inflammatory pain via TNF-α, IL6/MAPKScientific reports · 2026Article
- Traumatic brain injury-related ferroptosis: current perspectives.Journal of molecular medicine (Berlin, Germany) · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
introductionDepression is a prevalent and significant psychological consequence of traumatic brain injury (TBI). Ferroptosis, an iron-dependent form of regulated cell death, exacerbates the neurological damage associated with TBI. This study investigates whether nicorandil, a potassium channel opener with nitrate-like properties known for its antioxidative and neuroprotective effects, can mitigate depression-like behaviors following TBI by modulating ferroptosis.
methodsA controlled cortical impact (CCI) device was used to establish the TBI model. Depression-like behaviors in rats were assessed using the sucrose preference test (SPT), the tail suspension test (TST), and the forced swimming test (FST). The antioxidant system, lipid peroxidation, and ferroptosis levels were evaluated. The SLC7A11/GPX4 axis was analyzed using quantitative real-time PCR (qRT-PCR) and Western blot analysis.
resultsNicorandil administration significantly ameliorated depression-like behaviors in rats with TBI. Nicorandil administration also effectively restored the antioxidant system, substantially reduced lipid peroxidation, and attenuated ferroptosis in the hippocampus of rats with TBI. Mechanistically, nicorandil administration promoted the SLC7A11/GPX4 axis in the hippocampus of rats with TBI. Crucially, knockdown of hippocampal SLC7A11 abrogated the protective effects of nicorandil on depression-like behaviors, lipid peroxidation, and ferroptosis in the hippocampus of rats with TBI.
conclusionThese findings indicate that nicorandil ameliorates depression-like behaviors following TBI by inhibiting hippocampal ferroptosis through the activation of the SLC7A11/GPX4 axis.
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