ArticleBlood2011
Hyperhomocysteinemia increases permeability of the blood-brain barrier by NMDA receptor-dependent regulation of adherens and tight junctions.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 2 of them syntheses that pooled it.
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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
92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Homocysteine and cognitive function in depression: a systematic review and meta-analysis.Frontiers in psychiatry · 2026Pooled it
- Elevated Blood Homocysteine and Risk of Alzheimer's Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies.The journal of prevention of Alzheimer's diseasePooled it
- Baicalin and CNS-related diseases: new insights into neuroprotective potentials based on underlying mechanisms.Biochemistry and biophysics reports · 2026Review
- The Kidney-Brain Axis in Chronic Kidney Disease: Uremic Toxins, Cognitive Decline, Mechanistic Pathways, Biomarkers and Therapeutic Perspectives.Biomedicines · 2026Review
- Methionine, Homocysteine, and Methylation Levels Predict Cognitive Decline in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- Health Risk and Pathogenesis of PMToxics · 2026Review
- Neuroinflammation and blood-brain barrier dysfunction in cerebral small vessel disease: mechanisms, biomarkers, and therapeutic implications.European journal of medical research · 2026Review
- Association of serum and vitreous homocysteine and uric acid concentrations with post-vitrectomy prognosis in patients with proliferative diabetic retinopathy.World journal of diabetes · 2026Article
- Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.Nutrients · 2026Article
- Chronic stress and cognitive dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: HPA axis dysregulation and hippocampal plasticity.Frontiers in neuroscience · 2026Review
- Neighborhood deprivation and midlife cognition: Evidence of a modifiable vascular pathway involving health behaviors and cerebral small vessel disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression ofNeurobiology of stress · 2025Article
- Effects of modifying the pulse width on cognitive side effects with electroconvulsive therapy for schizophrenia.Schizophrenia research. Cognition · 2025Article
- Neuroprotective role of pyrroloquinoline quinone in folate deficiency-induced blood-brain barrier disruption.Fluids and barriers of the CNS · 2025Article
- Hyperhomocysteinemia-Driven Ischemic Stroke: Unraveling Molecular Mechanisms and Therapeutic Horizons.Food science & nutrition · 2025Review
- Lower water-soluble vitamins and higher homocysteine are associated with neurodegenerative diseases.Scientific reports · 2025Article
- Spaceflight Associated Neuro-ocular Syndrome (SANS) and its countermeasures.Progress in retinal and eye research · 2025Review
- The Role of Purinergic Mechanisms in the Excitability of Trigeminal Afferents of Rats with Prenatal Hyperhomocysteinemia.Biomolecules · 2025Article
- Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study.Neurology and therapy · 2025Article
- Association between serum uric acid levels and white matter hyperintensities in patients with mild ischemic stroke.Frontiers in neurology · 2025Article
32 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
3 authors at 1 institution in 1 country.
Funding
Abstract
Hyperhomocysteinemia (HHcy) increases permeability of the blood-brain barrier, but the mechanisms are undetermined. Homocysteine (Hcy) is an agonist of the neuronal N-methyl-D-aspartate receptor (NMDAr). We tested the hypothesis that HHcy disrupts the blood-brain barrier by an NMDAr-dependent mechanism in endothelium. In brain microvascular endothelial cells, there was no change in expression of the adherens junction protein VE-cadherin with Hcy treatment, but there was a significant decrease in the amount of β-catenin at the membrane. Moreover, Hcy caused nuclear translocation of β-catenin and attachment to the promoter for the tight junction protein claudin-5, with concomitant reduction in claudin-5 expression. Using a murine model of HHcy (cbs(+/-)), treatment for 2 weeks with an NMDAr antagonist (memantine) rescued cerebrovascular expression of claudin-5 and blood-brain barrier permeability to both exogenous sodium fluorescein and endogenous IgG. Memantine had no effect on these parameters in wild-type littermates. The same results were obtained using an in vitro model with brain microvascular endothelial cells. These data provide the first evidence that the NMDAr is required for Hcy-mediated increases in blood-brain barrier permeability. Modulating cerebral microvascular NMDAr activity may present a novel therapeutic target in diseases associated with opening of the blood-brain barrier in HHcy, such as stroke and dementia.
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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.