ArticleProceedings of the National Academy of Sciences of the United States of America2008
Key role of tissue plasminogen activator in neurovascular coupling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 92 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
- Cerebrovascular Dysfunction in Alzheimer's Disease and Transgenic Rodent Models.Journal of experimental neurology · 2024Article
- 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
- Two decades of astrocytes in neurovascular coupling.Frontiers in network physiology · 2023Review
- Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer's disease.Brain : a journal of neurology · 2022Article
- Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.Seminars in thrombosis and hemostasis · 2022Review
- Neuroserpin, a crucial regulator for axogenesis, synaptic modelling and cell-cell interactions in the pathophysiology of neurological disease.Cellular and molecular life sciences : CMLS · 2022Review
- Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury.Current neuropharmacology · 2021Review
- Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke.Frontiers in neurology · 2021Article
- The NGF Metabolic Pathway: New Opportunities for Biomarker Research and Drug Target Discovery : NGF Pathway Biomarkers and Drug Targets.Advances in experimental medicine and biology · 2021Article
- tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Tau induces PSD95-neuronal NOS uncoupling and neurovascular dysfunction independent of neurodegeneration.Nature neuroscience · 2020Article
- The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?Cellular and molecular life sciences : CMLS · 2019Review
- Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET-1 and JNK.Translational stroke research · 2019Article
- The Plasminogen Activation System Promotes Neurorepair in the Ischemic Brain.Current drug targets · 2019Review
- Worse Outcome in Stroke Patients Treated with rt-PA Without Early Reperfusion: Associated Factors.Translational stroke research · 2018Article
- Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- tPA Modulation of the Blood-Brain Barrier: A Unifying Explanation for the Pleiotropic Effects of tPA in the CNS.Seminars in thrombosis and hemostasis · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The increase in blood flow evoked by synaptic activity is essential for normal brain function and underlies functional brain imaging signals. Nitric oxide, a vasodilator released by NMDA receptor activation, is critical for the flow increase, but the factors linking NMDA receptor activity to nitric oxide-dependent hyperemia are poorly understood. Here, we show that tissue plasminogen activator (tPA), a serine protease implicated in NMDA receptor signaling, is required for the flow increase evoked by somatosensory stimulation. tPA acts by facilitating neuronal nitric oxide release, but this effect does not involve enhancement of NMDA currents or the associated intracellular Ca(2+) rise. Rather, the evidence suggests that tPA controls NMDA-dependent nitric oxide synthesis by influencing the phosphorylation state of neuronal nitric oxide synthase. These findings unveil a previously unrecognized role of tPA in vital homeostatic mechanisms coupling NMDA receptor signaling with nitric oxide synthesis and local cerebral perfusion.
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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.