ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Pharmacologically-induced neurovascular uncoupling is associated with cognitive impairment in mice.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.Ageing research reviews · 2023Pooled it
- Effects of NADThe Journal of pharmacology and experimental therapeutics · 2025Trial
- Network analysis identifies consensus physiological measures of neurovascular coupling in humans.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Trial
- Disturbed neurovascular coupling in type 2 diabetes mellitus patients: Evidence from a comprehensive fMRI analysis.NeuroImage. Clinical · 2019Trial
- ORAI CaScience signaling · 2026Article
- Translational difficulties in establishing a pharmacologically induced neurovascular uncoupling model in rats.Scientific reports · 2026Article
- Systems biology analysis of vasodynamics in mouse cerebral arterioles during resting state and functional hyperemia.PLoS computational biology · 2026Article
- Neurovascular decoupling: An early indicator of cognitive decline.Journal of Alzheimer's disease : JAD · 2026Article
- Maternal Apocynin During Experimental Preeclampsia Prevents BBB Permeability and Increased Vascular Tone of Cerebral Arteries in Male but Not Female Rat Adult Offspring.Microcirculation (New York, N.Y. : 1994) · 2026Article
- A Minimally Invasive Framework Reveals Region-Specific Cerebrovascular Remodeling in Aging Using Intravital Functional Ultrasound Imaging and Ultrasound Localization Microscopy (fUS-ULM).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chronic impairment of neurovascular coupling and cognitive decline in young survivors of severe traumatic brain injury.GeroScience · 2025Article
- Neurovascular coupling abnormalities in first-episode drug-naïve major depressive disorder patients.BMC psychiatry · 2025Article
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
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- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- The vascular contribution to cognitive decline in ageing and dementia.Nature reviews. Neuroscience · 2025Review
- Sleep Disorders and Stroke: Pathophysiological Links, Clinical Implications, and Management Strategies.Medical sciences (Basel, Switzerland) · 2025Review
- Cerebral blood flow and energy demand: imaging insights into neurovascular function.Neurophotonics · 2025Review
- Article
- Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
There is increasing evidence that vascular risk factors, including aging, hypertension, diabetes mellitus, and obesity, promote cognitive impairment; however, the underlying mechanisms remain obscure. Cerebral blood flow (CBF) is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism is known to be impaired in the aforementioned pathophysiologic conditions. To establish a direct relationship between impaired NVC and cognitive decline, we induced neurovascular uncoupling pharmacologically in mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH), the NO synthase inhibitor l-NG-Nitroarginine methyl ester (L-NAME), and the COX inhibitor indomethacin decreased NVC by over 60% mimicking the aging phenotype, which was associated with significantly impaired spatial working memory (Y-maze), recognition memory (Novel object recognition), and impairment in motor coordination (Rotarod). Blood pressure (tail cuff) and basal cerebral perfusion (arterial spin labeling perfusion MRI) were unaffected. Thus, selective experimental disruption of NVC is associated with significant impairment of cognitive and sensorimotor function, recapitulating neurologic symptoms and signs observed in brain aging and pathophysiologic conditions associated with accelerated cerebromicrovascular aging.
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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.