ArticleStroke2012
Chronic valproate treatment enhances postischemic angiogenesis and promotes functional recovery in a rat model of ischemic stroke.
Article in Stroke, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.
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
77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Role of histone deacetylases and sirtuins in the ischaemic stroke: a systematic review and meta-analysis of animal studies.Stroke and vascular neurology · 2026Pooled it
- Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.Translational research : the journal of laboratory and clinical medicine · 2019Pooled it
- Brain-Derived Cystathionine β-Synthase-Generated HCurrent issues in molecular biology · 2026Article
- CX3CL1/CX3CR1 axis dysregulation contributes to epileptogenic mechanisms in focal cortical dysplasia.Acta neuropathologica communications · 2026Article
- Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- Sodium Valproate Mitigates Hippocampal Structural and Functional Alterations Following Middle Cerebral Artery Occlusion in a Rat Model.Basic and clinical neuroscience · 2025Article
- Article
- Valproic Acid Inhibits RhoA-Mediated Vascular Smooth Muscle Cell Contraction.Journal of Korean medical science · 2025Article
- Integrated Strategies for Targeting Arteriogenesis and Angiogenesis After Stroke.Translational stroke research · 2025Review
- Protective effect of valproic acid on ischemia-reperfusion induced spinal cord injury in a rat model.The journal of spinal cord medicine · 2024Article
- Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Personalized, Precision Medicine to Cure Alzheimer's Dementia: Approach #1.International journal of molecular sciences · 2024Review
- Valproic acid and/or rapamycin preconditioning protects hair follicle stem cells from oxygen glucose serum deprivation-induced oxidative injury via activating Nrf2 pathway.Molecular biology research communications · 2024Article
- Crosstalk Between Autophagy and Inflammation in Chronic Cerebral Ischaemia.Cellular and molecular neurobiology · 2023Review
- A comprehensive review on pharmacological applications and drug-induced toxicity of valproic acid.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Anti-Epileptic Medication Exposure Influences Functional Status in New Zealand Stroke Patients: A Retrospective Population-Level Study.Drugs - real world outcomes · 2022Article
- Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice.International journal of molecular sciences · 2022Article
- 1α,25-Dihydroxyvitamin D3 Promotes Angiogenesis After Cerebral Ischemia Injury in Rats by Upregulating the TGF-β/Smad2/3 Signaling Pathway.Frontiers in cardiovascular medicine · 2022Article
- The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke.Neuromolecular medicine · 2021Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
background and purposeEnhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke.
methodsMale rats underwent middle cerebral artery occlusion for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function through the Rotarod test; infarct volume through T2-weighted MRI; microvessel density through immunohistochemistry; relative cerebral blood flow through perfusion-weighted imaging; protein levels of proangiogenic factors through Western blotting; and matrix metalloproteinase-2/9 activities through gelatin zymography.
resultsPostischemic VPA treatment robustly improved the Rotarod performance of middle cerebral artery occlusion rats on Days 7 and 14 after ischemia and significantly reduced brain infarction on Day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased relative cerebral blood flow in the ipsilateral cortex. The transcription factor hypoxia-inducible factor-1α and its downstream proangiogenic factors, vascular endothelial growth factor and matrix metalloproteinase-2/9, were upregulated after middle cerebral artery occlusion and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on Rotarod performance and microvessel density were abolished by hypoxia-inducible factor-1α inhibition.
conclusionsChronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve histone deacetylase inhibition and upregulation of hypoxia-inducible factor-1α and its downstream proangiogenic factors vascular endothelial growth factor and matrix metalloproteinase-2/9.
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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.