ArticleMolecular neurobiology2019
Resveratrol Preconditioning Induces Genomic and Metabolic Adaptations within the Long-Term Window of Cerebral Ischemic Tolerance Leading to Bioenergetic Efficiency.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Resveratrol and Curcumin in Stroke Therapy: From Experimental Evidence to Clinical Perspectives.Nutrients · 2026Review
- Regulatory Dynamics of Nrf2 With Sirtuins in the Brain: Exploring Cellular Metabolism, Synaptic Plasticity, and Defense Mechanisms.Journal of neurochemistry · 2025Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Recurrent hypoglycemia exposure increases the risk of platelet activation and thrombosis in insulin-treated diabetic rats.Diabetes, obesity & metabolism · 2025Article
- Role of mitochondrial metabolism in ischemic stroke and natural products intervention.Molecular biology reports · 2025Review
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- The therapeutic effects and mechanisms of glucagon-like peptide-1 receptor agonists in neurocognitive disorders.Therapeutic advances in neurological disorders · 2025Review
- Resveratrol Mitigates Cognitive Impairments and Cholinergic Cell Loss in the Medial Septum in a Mouse Model of Gradual Cerebral Hypoperfusion.Antioxidants (Basel, Switzerland) · 2024Article
- Resveratrol Preconditioning Downregulates PARP1 Protein to Alleviate PARP1-Mediated Cell Death Following Cerebral Ischemia.Translational stroke research · 2024Article
- Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery.Frontiers in pharmacology · 2024Review
- Neuroprotective Agents with Therapeutic Potential for COVID-19.Biomolecules · 2023Review
- Potential Role of Natural Antioxidants in Countering Reperfusion Injury in Acute Myocardial Infarction and Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2023Review
- Resveratrol Preconditioning Protects Against Ischemia-Induced Synaptic Dysfunction and Cofilin Hyperactivation in the Mouse Hippocampal Slice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.CNS neuroscience & therapeutics · 2023Article
- Targeting pyroptosis as a preventive and therapeutic approach for stroke.Cell death discovery · 2023Review
- Post cardiac arrest physical exercise mitigates cell death in the septal and thalamic nuclei and ameliorates contextual fear conditioning deficits in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain.International journal of molecular sciences · 2022Review
- Polyphenols for the Treatment of Ischemic Stroke: New Applications and Insights.Molecules (Basel, Switzerland) · 2022Review
- Antioxidant and neuroprotective actions of resveratrol in cerebrovascular diseases.Frontiers in pharmacology · 2022Review
- Mitochondria as the memory of preconditioning.Conditioning medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroprotective agents administered post-cerebral ischemia have failed so far in the clinic to promote significant recovery. Thus, numerous efforts were redirected toward prophylactic approaches such as preconditioning as an alternative therapeutic strategy. Our laboratory has revealed a novel long-term window of cerebral ischemic tolerance mediated by resveratrol preconditioning (RPC) that lasts for 2 weeks in mice. To identify its mediators, we conducted an RNA-seq experiment on the cortex of mice 2 weeks post-RPC, which revealed 136 differentially expressed genes. The majority of genes (116/136) were downregulated upon RPC and clustered into biological processes involved in transcription, synaptic signaling, and neurotransmission. The downregulation in these processes was reminiscent of metabolic depression, an adaptation used by hibernating animals to survive severe ischemic states by downregulating energy-consuming pathways. Thus, to assess metabolism, we used a neuronal-astrocytic co-culture model and measured the cellular respiration rate at the long-term window post-RPC. Remarkably, we observed an increase in glycolysis and mitochondrial respiration efficiency upon RPC. We also observed an increase in the expression of genes involved in pyruvate uptake, TCA cycle, and oxidative phosphorylation, all of which indicated an increased reliance on energy-producing pathways. We then revealed that these nuclear and mitochondrial adaptations, which reduce the reliance on energy-consuming pathways and increase the reliance on energy-producing pathways, are epigenetically coupled through acetyl-CoA metabolism and ultimately increase baseline ATP levels. This increase in ATP would then allow the brain, a highly metabolic organ, to endure prolonged durations of energy deprivation encountered during cerebral ischemia.
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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.