ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2020
Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Inhibition of tPA-NMDAR interaction prevents neurovascular and functional deficits induced by organophosphorus nerve agents.Cell death and differentiation · 2026Article
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- NP10679: A new horizon for neuroprotection in aneurysmal subarachnoid hemorrhage.The Journal of pharmacology and experimental therapeutics · 2025Article
- Waste clearance shapes aging brain health.Neuron · 2025Review
- Review
- Article
- The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator.Journal of personalized medicine · 2023Review
- The Emerging Role of N-Methyl-D-Aspartate (NMDA) Receptors in the Cardiovascular System: Physiological Implications, Pathological Consequences, and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors.Fluids and barriers of the CNS · 2023Article
- Modulations of the neuronal trafficking of tissue-type plasminogen activator (tPA) influences glutamate release.Cell death & disease · 2023Article
- Two decades of astrocytes in neurovascular coupling.Frontiers in network physiology · 2023Review
- Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction.Frontiers in molecular neuroscience · 2023Review
- tPA-NMDAR Signaling Blockade Reduces the Incidence of Intracerebral Aneurysms.Translational stroke research · 2022Article
- A role for endothelial NMDA receptors in the pathophysiology of schizophrenia.Schizophrenia research · 2022Review
- [The developments and applications of functional ultrasound imaging].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2022Review
- The choroid plexus: a door between the blood and the brain for tissue-type plasminogen activator.Fluids and barriers of the CNS · 2022Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.Seminars in thrombosis and hemostasis · 2022Review
- Article
- Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke.Frontiers in neurology · 2021Article
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increase of cerebral blood flow evoked by neuronal activity is essential to ensure enough energy supply to the brain. In the neurovascular unit, endothelial cells are ideally placed to regulate key neurovascular functions of the brain. Nevertheless, some outstanding questions remain about their exact role neurovascular coupling (NVC). Here, we postulated that the tissue-type plasminogen activator (tPA) present in the circulation might contribute to NVC by a mechanism dependent of its interaction with endothelial N-Methyl-D-Aspartate Receptor (NMDAR). To address this question, we used pharmacological and genetic approaches to interfere with vascular tPA-dependent NMDAR signaling, combined with laser speckle flowmetry, intravital microscopy and ultrafast functional ultrasound in vivo imaging. We found that the tPA present in the blood circulation is capable of potentiating the cerebral blood flow increase induced by the activation of the mouse somatosensorial cortex, and that this effect is mediated by a tPA-dependent activation of NMDAR expressed at the luminal part of endothelial cells of arteries. Although blood molecules, such as acetylcholine, bradykinin or ATP are known to regulate vascular tone and induce vessel dilation, our present data provide the first evidence that circulating tPA is capable of influencing neurovascular coupling (NVC).
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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.