ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2013
Induction of hyperhomocysteinemia models vascular dementia by induction of cerebral microhemorrhages and neuroinflammation.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 140 citations in OpenAlex.
- Diet-Induced Hyperhomocysteinemia in C57BL/6 Mice: Simultaneous Evaluation of Plasma Homocysteine, Methionine, and Cysteine by LC-MS/MS and Assessment of Associated Oxidative Stress in Brain Homogenates.Antioxidants (Basel, Switzerland) · 2026Article
- Protective effects of ginsenosides in cerebral small vessel disease: Cellular and molecular mechanisms.Journal of ginseng research · 2025Review
- Integrative proteomic and metabolomic analysis reveals the mechanisms underlying ischemic stroke induced by vitamin B12 deficiency.European journal of nutrition · 2025Article
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Cerebrovascular p16Acta neuropathologica communications · 2025Article
- Inhibition of astrocyte signaling leads to sex-specific changes in microglia phenotypes in a diet-based model of cerebral small vessel disease.Journal of neuroinflammation · 2025Article
- Retinal vascular dysfunction in the MthfrAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Review
- Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.Journal of neuroinflammation · 2025Article
- A small molecule p38α MAPK inhibitor, MW150, attenuates behavioral deficits and neuronal dysfunction in a mouse model of mixed amyloid and vascular pathologies.Brain, behavior, & immunity - health · 2024Article
- Homocysteine potentiates amyloidAging cell · 2024Article
- Metformin role in Parkinson's disease: a double-sword effect.Molecular and cellular biochemistry · 2024Review
- Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model.Heliyon · 2024Article
- Comprehensive predictive model for cerebral microbleeds: integrating clinical and biochemical markers.Frontiers in neuroscience · 2024Article
- The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment.Nutrients · 2023Review
- Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage by downregulating pCAMK2A.Stroke and vascular neurology · 2023Article
- Chronic cerebral hypoperfusion: a critical feature in unravelling the etiology of vascular cognitive impairment.Acta neuropathologica communications · 2023Review
- Targeting Astrocyte Signaling Alleviates Cerebrovascular and Synaptic Function Deficits in a Diet-Based Mouse Model of Small Cerebral Vessel Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- TheJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Vascular dementia (VaD) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent comorbidity with AD, estimated to occur in as many as 40% of AD patients. The causes of VaD are varied and include chronic cerebral hypoperfusion, microhemorrhages, hemorrhagic infarcts, or ischemic infarcts. We have developed a model of VaD by inducing hyperhomocysteinemia (HHcy) in wild-type mice. By placing wild-type mice on a diet deficient in folate, B6, and B12 and supplemented with excess methionine, we induced a moderate HHcy (plasma level homocysteine 82.93 ± 3.561 μmol). After 11 weeks on the diet, the hyperhomocysteinemic mice showed a spatial memory deficit as assessed by the 2-day radial-arm water maze. Also, magnetic resonance imaging and subsequent histology revealed significant microhemorrhage occurrence. We found neuroinflammation induced in the hyperhomocysteinemic mice as determined by elevated interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 in brain tissue. Finally, we found increased expression and increased activity of the matrix metalloproteinase 2 (MMP2) and MMP9 systems that are heavily implicated in the pathogenesis of cerebral hemorrhage. Overall, we have developed a dietary model of VaD that will be valuable for studying the pathophysiology of VaD and also for studying the comorbidity of VaD with other dementias and other neurodegenerative disorders.
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