ArticleRedox biology2023
Targeting succinate metabolism to decrease brain injury upon mechanical thrombectomy treatment of ischemic stroke.
Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- PreclinicalMagnetic resonance in medicine · 2026Article
- Advances in metabolomics of biomarkers for ischemic stroke: From bench to clinic.Neural regeneration research · 2026Article
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Article
- Widely targeted metabolomics and machine learning identify succinate as a key metabolite in sepsis-associated encephalopathy.iScience · 2026Article
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
- [Role of succinylation modification in central nervous system diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- High-Resolution Spatiotemporal Mapping of Cerebral Metabolism During Middle-Cerebral-Artery Occlusion/Reperfusion Progression: Preliminary Insights.Biomolecules · 2025Article
- Alpha-ketoglutarate protects against myocardial infarction via FTO-mediated anti-inflammatory macrophage activation.Basic research in cardiology · 2025Article
- From Mechanisms to Diseases: The Succinate-GPR91 Axis in Cardiometabolic Diseases.Journal of cardiovascular translational research · 2025Review
- Rescuing Ischemic Brain Injury by Rewiring Mitochondrial Electron Flow.bioRxiv : the preprint server for biology · 2025Article
- Succinate Dehydrogenase Subunit A (SDHA) Mediated Microglia Extracellular Traps Formation Participating in Cerebral Ischemic Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of HINT3 in Myocardial Ischemia-Reperfusion Injury in Male Mice: Mechanisms Involving SDHA and its Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischemic stroke.Cardiovascular research · 2025Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Plasma succinate and the risks of cardiovascular events and recurrent stroke after ischemic stroke: A nested case-control study.Chinese medical journal · 2025Article
- Role of mitochondrial metabolism in ischemic stroke and natural products intervention.Molecular biology reports · 2025Review
- An integrated bioinformatic investigation of succinic acid metabolism related genes in ccRCC followed by preliminary validation of SLC25A4 in tumorigenesis.Scientific reports · 2025Article
- Brain Adenylosuccinate Is Dramatically Increased Under Global Ischemia Without Evidence for Purine Nucleotide Cycle Activation.Journal of neurochemistry · 2025Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Current treatments for acute ischemic stroke aim to reinstate a normal perfusion in the ischemic territory but can also cause significant ischemia-reperfusion (IR) injury. Previous data in experimental models of stroke show that ischemia leads to the accumulation of succinate, and, upon reperfusion, the accumulated succinate is rapidly oxidized by succinate dehydrogenase (SDH) to drive superoxide production at mitochondrial complex I. Despite this process initiating IR injury and causing further tissue damage, the potential of targeting succinate metabolism to minimize IR injury remains unexplored. Using both quantitative and untargeted high-resolution metabolomics, we show a time-dependent accumulation of succinate in both human and mouse brain exposed to ischemia ex vivo. In a mouse model of ischemic stroke/mechanical thrombectomy mass spectrometry imaging (MSI) shows that succinate accumulation is confined to the ischemic region, and that the accumulated succinate is rapidly oxidized upon reperfusion. Targeting succinate oxidation by systemic infusion of the SDH inhibitor malonate upon reperfusion leads to a dose-dependent decrease in acute brain injury. Together these findings support targeting succinate metabolism upon reperfusion to decrease IR injury as a valuable adjunct to mechanical thrombectomy in ischemic stroke.
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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.