ArticleProceedings of the National Academy of Sciences of the United States of America2015
Endothelial depletion of murine SRF/MRTF provokes intracerebral hemorrhagic stroke.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- Predicting intracranial hypertension as a secondary insult using the pathological peptidome of brain injured patients.Scientific reports · 2026Article
- Spatial Transcriptomics and Dual Dye Mapping Identify Wnt-Driven BBB Protection in Endothelial EphA4-Deficiency.Research square · 2026Article
- Blood-Brain Barrier Disruption and Imaging Assessment in Stroke.Translational stroke research · 2025Review
- miRNA in blood-brain barrier repair: role of extracellular vesicles in stroke recovery.Frontiers in cellular neuroscience · 2025Review
- Resveratrol: a potential medication for the prevention and treatment of varicella zoster virus-induced ischemic stroke.European journal of medical research · 2023Article
- Age-Associated Changes in Endothelial Transcriptome and Epigenetic Landscapes Correlate With Elevated Risk of Cerebral Microbleeds.Journal of the American Heart Association · 2023Article
- Ischemia Reperfusion Injury Induced Blood Brain Barrier Dysfunction and the Involved Molecular Mechanism.Neurochemical research · 2023Review
- Cerebrovascular GMolecular imaging and biology · 2023Article
- Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.Stroke · 2023Review
- Blood-Brain Barrier Dysfunction in the Pathogenesis of Major Depressive Disorder.Cellular and molecular neurobiology · 2022Review
- Multiparametric Longitudinal Profiling of RCAS-tva-Induced PDGFB-Driven Experimental Glioma.Brain sciences · 2022Article
- Mechanical regulation of chromatin and transcription.Nature reviews. Genetics · 2022Review
- Dysfunction of the Blood-brain Barrier in Cerebral Microbleeds: from Bedside to Bench.Aging and disease · 2021Review
- NG2/CSPG4, CD146/MCAM and VAP1/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells.Scientific reports · 2021Article
- Machine learning identifies stroke features between species.Theranostics · 2021Article
- Regulation of the Muscarinic MFrontiers in physiology · 2021Article
- A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina.iScience · 2020Article
- Selective protection of murine cerebral GJournal of molecular medicine (Berlin, Germany) · 2020Article
- Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracerebral hemorrhagic stroke and vascular dementia are age- and hypertension-associated manifestations of human cerebral small vessel disease (SVD). Cerebral microvessels are formed by endothelial cells (ECs), which are connected through tight junctions, adherens junctions, and stabilizing basement membrane structures. These endothelial connections ensure both vessel stability and blood-brain barrier (BBB) functions, the latter enabling selective exchange of ions, bioactive molecules, and cells between the bloodstream and brain tissue. Srf(iECKO) mice, permitting conditional EC-specific depletion of the transcription factor Serum Response Factor (SRF), suffer from loss of BBB integrity and intracerebral hemorrhaging. Cerebral microbleeds and larger hemorrhages developed upon postnatal and adult depletion of either SRF or its cofactors Myocardin Related Transcription Factor (MRTF-A/-B), revealing essential requirements of ongoing SRF/MRTF activity for maintenance of cerebral small vessel integrity. In vivo magnetic resonance imaging allowed detection, localization, and time-resolved quantification of BBB permeability and hemorrhage formation in Srf(iECKO) brains. At the molecular level, direct and indirect SRF/MRTF target genes, encoding structural components of tight junctions (Claudins and ZO proteins), adherens junctions (VE-cadherin, α-Actinin), and the basement membrane (Collagen IV), were down-regulated upon SRF depletion. These results identify SRF and its MRTF cofactors as major transcriptional regulators of EC junctional stability, guaranteeing physiological functions of the cerebral microvasculature. We hypothesize that impairments in SRF/MRTF activity contribute to human SVD pathology.
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