ArticleMolecular neurodegeneration2015
Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Integrative analyses of genes related to femoral head osteonecrosis: an umbrella review of systematic reviews and meta-analyses of observational studies.Journal of orthopaedic surgery and research · 2022Pooled it
- Biomarker advancements in cerebral small vessel disease: An overview.Neural regeneration research · 2026Article
- Endothelial TRIM47 regulates blood-brain barrier integrity and cognition via the KEAP1/NRF2 signalling pathway in mice.Communications biology · 2026Article
- The neurobiological regulatory mechanism of brain edema.Frontiers in cellular neuroscience · 2026Review
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
- Critical Role of the Endothelial αV/β5 Integrin Receptor Signaling Pathway in Promoting Irisin-induced Hippocampal BDNF Expression.Molecular neurobiology · 2025Article
- Cerebrovascular protective functions of amyloid precursor protein: Progress and therapeutic prospects.Pharmacology & therapeutics · 2025Review
- FAD012, a Ferulic Acid Derivative, Preserves Cerebral Blood Flow and Blood-Brain Barrier Integrity in the Rat Photothrombotic Stroke Model.Biomedicines · 2025Article
- Partial eNOS Deficiency Results in Greater Levels of Vascular Inflammation and BBB Disruption in Response to Chronic Mild Hypoxia.International journal of molecular sciences · 2025Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- SARS-CoV-2 (MA10) Infection Aggravates Cerebrovascular Pathology in Endothelial Nitric Oxide Synthase-Deficient Mice.Viruses · 2025Article
- Endothelial cells as key players in cerebral small vessel disease.Nature reviews. Neuroscience · 2025Review
- Mirodenafil improves cognitive function by reducing microglial activation and blood-brain barrier permeability in ApoE4 KI mice.Frontiers in aging neuroscience · 2025Article
- Roles of neuroimaging markers and biomarkers in cerebral small vessel disease and their associations with cognitive function.Frontiers in neurology · 2025Review
- Chronic stress in adulthood results in microvascular dysfunction and subsequent depressive-like behavior.Scientific reports · 2024Article
- The Cerebrovascular Side of Plasticity: Microvascular Architecture across Health and Neurodegenerative and Vascular Diseases.Brain sciences · 2024Review
- The Influence of Oxidative Stress Markers in Patients with Ischemic Stroke.Biomolecules · 2024Review
- ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging.Kidney international · 2024Article
- Cerebrovascular Endothelial Dysfunction: Role of BACE1.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Cellular Components of the Blood-Brain Barrier and Their Involvement in Aging-Associated Cognitive Impairment.Aging and disease · 2024Review
17 more citing papers are in PubMed but not listed here.
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10 authors at 3 institutions in 2 countries.
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Abstract
backgroundCerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels.
resultsCombining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice.
conclusionsThese data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.
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