ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Poly(ADP-ribose) polymerase-1 inhibition in brain endothelium protects the blood-brain barrier under physiologic and neuroinflammatory conditions.
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 43 papers.
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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
43 citing papers in PubMed, 70 citations in OpenAlex.
- First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of a Neuroprotective Poly (ADP-ribose) Polymerase-1 Inhibitor, JPI-289, in Healthy Volunteers.Drug design, development and therapy · 2020Trial
- Orally bioavailable CBResearch square · 2026Article
- Diversity of Brain Microvascular Endothelial Cell Functions: Physiology, Ischemia/Hypoxia, and Underlying Protection.Aging and disease · 2025Review
- Emergence of cyclic hypoxia and the impact of PARP inhibitors on tumor progression.NPJ systems biology and applications · 2024Article
- Amyloid Beta-Mediated Neurovascular Toxicity in Alzheimer's Disease.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Glitches in the brain: the dangerous relationship between radiotherapy and brain fog.Frontiers in cellular neuroscience · 2024Review
- Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain.ACS nano · 2023Article
- Role of NADCellular and molecular neurobiology · 2023Review
- Melatonin Is Neuroprotective inInternational journal of molecular sciences · 2022Article
- Activation of peripheral TRPM8 mitigates ischemic stroke by topically applied menthol.Journal of neuroinflammation · 2022Article
- Poly (ADP-ribose) polymerases as PET imaging targets for central nervous system diseases.Frontiers in medicine · 2022Review
- miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Combination of HIV-1 and Diabetes Enhances Blood Brain Barrier Injury via Effects on Brain Endothelium and Pericytes.International journal of molecular sciences · 2020Article
- Hyperglycemia and advanced glycation end products disrupt BBB and promote occludin and claudin-5 protein secretion on extracellular microvesicles.Scientific reports · 2020Article
- Effects of Drugs of Abuse on the Blood-Brain Barrier: A Brief Overview.Frontiers in neuroscience · 2020Review
- The Blood-Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders.International journal of molecular sciences · 2019Review
- Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide.Metabolomics : Official journal of the Metabolomic Society · 2019Review
- Poster Viewing Sessions PB01-B01 to PB03-V09.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Synthetic cathinone MDPV enhances reward function through purinergic P2X7 receptor-dependent pathway and increases P2X7 gene expression in nucleus accumbens.Drug and alcohol dependence · 2019Article
- Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity.Microbiology and molecular biology reviews : MMBR · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Blood-brain barrier (BBB) dysfunction seen in neuroinflammation contributes to mortality and morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. Identification of molecular targets maintaining barrier function is of clinical relevance. We used a novel in vivo model of localized aseptic meningitis where tumor necrosis factor alpha (TNFα) was introduced intracerebrally and surveyed cerebral vascular changes and leukocyte-endothelium interactions by intravital videomicroscopy. Poly(ADP-ribose) polymerase-1 (PARP) inhibition significantly reduced leukocyte adhesion to and migration across brain endothelium in cortical microvessels. PARP inactivation diminished BBB permeability in an in vivo model of systemic inflammation. PARP suppression in primary human brain microvascular endothelial cells (BMVEC), an in vitro model of BBB, enhanced barrier integrity and augmented expression of tight junction proteins. PARP inhibition in BMVEC diminished human monocyte adhesion to TNFα-activated BMVEC (up to 65%) and migration (80-100%) across BBB models. PARP suppression decreased expression of adhesion molecules and decreased activity of GTPases (controlling BBB integrity and monocyte migration across the BBB). PARP inhibitors down-regulated expression of inflammatory genes and dampened secretion of pro-inflammatory factors increased by TNFα in BMVEC. These results point to PARP suppression as a novel approach to BBB protection in the setting of endothelial dysfunction caused by inflammation.
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What OpenQuestion holds
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.