ArticleBritish journal of pharmacology2017
NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tissue plasminogen activator-induced haemorrhagic transformation after cerebral ischaemia.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- Mortality, functional outcome, and bleeding risk after early versus delayed thrombectomy.GeroScience · 2026Pooled it
- Protective Effects of Nicotinamide Adenine Dinucleotide and Related Precursors in Alzheimer's Disease: A Systematic Review of Preclinical Studies.Journal of molecular neuroscience : MN · 2021Pooled it
- Proteoglycan 4 attenuates ischemic post-stroke hemorrhagic transformation and blood-brain barrier disruption.IBRO neuroscience reports · 2025Article
- Network of nicotinamide mononucleotide biosynthesis: substrate tracking, rate-limiting enzyme, and regulatory strategy.Synthetic and systems biotechnology · 2025Review
- Molecular Mediators of Neutrophil Primary Granule Release Following Acute Ischemic Stroke and their Associated Epigenetic Modulation by HDAC2.Molecular neurobiology · 2025Article
- NMN Supplementation Inhibits Endothelial Cell ROS-Mediated Src/Pi3k/Akt Signaling Pathway to Protect High-Altitude Blood-Retinal Barrier.Investigative ophthalmology & visual science · 2025Article
- Brain-Targeting Emodin Mitigates Ischemic Stroke via Inhibiting AQP4-Mediated Swelling and Neuroinflammation.Translational stroke research · 2024Article
- Propofol Suppresses LPS-induced BBB Damage by Regulating miR-130a-5p/ZO-1 Axis.Molecular biotechnology · 2024Article
- Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications.Metabolites · 2024Review
- The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update.Advances in nutrition (Bethesda, Md.) · 2023Review
- The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator.Journal of personalized medicine · 2023Review
- Role of NADCellular and molecular neurobiology · 2023Review
- The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study.Frontiers in cellular neuroscience · 2023Article
- Distribution of Nicotinamide Mononucleotide after Intravenous Injection in Normal and Ischemic Stroke Mice.Current pharmaceutical biotechnology · 2023Article
- Nicotinamide Mononucleotide Adenylyltransferase 1 Regulates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption Through NADMolecular neurobiology · 2022Article
- Nicotinamide Mononucleotide Prevents Cisplatin-Induced Mitochondrial Defects in Cortical Neurons Derived from Human Induced Pluripotent Stem Cells.Brain plasticity (Amsterdam, Netherlands) · 2022Article
- Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors.Aging and disease · 2021Review
- Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia.Stroke and vascular neurology · 2021Article
- Potential therapeutic effects of Nrf2 activators on intracranial hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- NADNature reviews. Molecular cell biology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeTissue plasminogen activator (tPA) is the only approved pharmacological therapy for acute brain ischaemia; however, a major limitation of tPA is the haemorrhagic transformation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. EXPERIMENTAL APPROACH: Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h. When the filament was removed for reperfusion, tPA was infused via the tail vein. A single dose of NMN was injected i.p. (300 mg·kg KEY
resultsIn the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1, and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.
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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.