ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2014
Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2014. 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.
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Sex-specific implications of inflammation in covert cerebral small vessel disease.BMC neurology · 2024Article
- Dietary vitamin B6 intake and stroke are negatively associated in adults: A cross-sectional study from the NHANES.Heliyon · 2024Article
- Cellular junction dynamics and Alzheimer's disease: a comprehensive review.Molecular biology reports · 2024Review
- AGEs promote atherosclerosis by increasing LDL transcytosis across endothelial cells via RAGE/NF-κB/Caveolin-1 pathway.Molecular medicine (Cambridge, Mass.) · 2023Article
- The Role of Nuclear Factor-Kappa B in Fibrinogen-Induced Inflammatory Responses in Cultured Primary Neurons.Biomolecules · 2022Article
- Review
- Key brain cell interactions and contributions to the pathogenesis of Alzheimer's disease.Frontiers in cell and developmental biology · 2022Review
- Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline-A Review.Biomolecules · 2021Review
- Effects of fibrinogen synthesis inhibition on vascular cognitive impairment during traumatic brain injury in mice.Brain research · 2021Article
- Endothelial Dysfunction and Hyperhomocysteinemia-Linked Cerebral Small Vessel Disease: Underlying Mechanisms and Treatment Timing.Frontiers in neurology · 2021Review
- Fibrinogen-cellular prion protein complex formation on astrocytes.Journal of neurophysiology · 2020Article
- Homocysteine Impairs Endothelial Cell Barrier Function and Angiogenic Potential via the Progranulin/EphA2 Pathway.Frontiers in pharmacology · 2020Article
- Effect ofPhysiological genomics · 2019Article
- Vascular and non-vascular contributors to memory reduction during traumatic brain injury.The European journal of neuroscience · 2019Review
- Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen.International journal of molecular sciences · 2019Article
- High methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet causes neurodegeneration and subsequent short-term memory loss.Metabolic brain disease · 2018Article
- Hyperfibrinogenemia-mediated astrocyte activation.Brain research · 2018Article
- The blood-brain barrier in Alzheimer's disease.Neurobiology of disease · 2017Review
- Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2017Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen-β-amyloid (Fg-Aβ) complex. Cerebrovascular permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine-β-synthase heterozygote (Cbs+/-, a genetic model of HHcy), MMP9 gene knockout (Mmp9-/-), and Cbs and Mmp9 double knockout (Cbs+/-/Mmp9-/-) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-Aβ complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs+/- mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-Aβ complex formation was the highest along with the diminished short-term memory in Cbs+/- mice. These effects of HHcy were ameliorated in Cbs+/-/Mmp9-/- mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-Aβ complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies.
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