ArticleBrain : a journal of neurology2022
VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer's mice.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 85 citations in OpenAlex.
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- Compartmentalized VEGF receptor expression in hypothalamic tanycytes reveals a novel non-endothelial axis of VEGF signaling : Tanycytes as a novel non-endothelial target of VEGF signaling.Fluids and barriers of the CNS · 2026Article
- Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.Drug design, development and therapy · 2026Review
- Post-marketing safety of lecanemab: a real-world study based on FAERS database, multicenter cohort and network pharmacology.Frontiers in psychiatry · 2026Article
- Neutrophil stalling does not mediate the increase in tau phosphorylation and the cognitive impairment associated with high salt diet.Cardiovascular research · 2025Article
- Systemic Piezo1 activation improves cerebrovascular function in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Transferrin receptor-binding blood-brain barrier shuttle enhances brain delivery and plaque-clearing efficacy of a therapeutic anti-Aβ antibody.Fluids and barriers of the CNS · 2025Article
- Memory deficits in hypertensive ApoE4 mice reversed by P2Y12 inhibition via different mechanisms in males and perimenopausal females.Research square · 2025Article
- Cerebrovascular p16Acta neuropathologica communications · 2025Article
- Oral Prodrug of a Novel Glutathione Surrogate Reverses Metabolic Dysregulation and Attenuates Neurodegenerative Process in Transgenic Alzheimer's Mice.ACS pharmacology & translational science · 2025Article
- Sex-specific association between body roundness index and cognitive impairment among hospitalized middle-aged and elderly patients with type 2 diabetes in China: a cross-sectional analysis.European journal of medical research · 2025Article
- Machine learning-based method to detect capillary stalling using optical coherence tomography.Biomedical optics express · 2025Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Increased incidence of stalled capillary blood flow caused by adhesion of leucocytes to the brain microvascular endothelium leads to a 17% reduction of cerebral blood flow and exacerbates short-term memory loss in multiple mouse models of Alzheimer's disease. Here, we report that vascular endothelial growth factor (VEGF) signalling at the luminal side of the brain microvasculature plays an integral role in the capillary stalling phenomenon of the APP/PS1 mouse model. Administration of the anti-mouse VEGF-A164 antibody, an isoform that inhibits blood-brain barrier hyperpermeability, reduced the number of stalled capillaries within an hour of injection, leading to an immediate increase in average capillary blood flow but not capillary diameter. VEGF-A inhibition also reduced the overall endothelial nitric oxide synthase protein concentrations, increased occludin levels and decreased the penetration of circulating Evans Blue dye across the blood-brain barrier into the brain parenchyma, suggesting increased blood-brain barrier integrity. Capillaries prone to neutrophil adhesion after anti-VEGF-A treatment also had lower occludin concentrations than flowing capillaries. Taken together, our findings demonstrate that VEGF-A signalling in APP/PS1 mice contributes to aberrant endothelial nitric oxide synthase /occludin-associated blood-brain barrier permeability, increases the incidence of capillary stalls, and leads to reductions in cerebral blood flow. Reducing leucocyte adhesion by inhibiting luminal VEGF signalling may provide a novel and well-tolerated strategy for improving brain microvascular blood flow in Alzheimer's disease patients.
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