ArticleJournal of neuroinflammation2016
PARP inhibition in leukocytes diminishes inflammation via effects on integrins/cytoskeleton and protects the blood-brain barrier.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.Translational oncology · 2026Review
- Poly(ADP-ribose) polymerase 1 orchestrates vascular smooth muscle cell homeostasis in arterial disease.Experimental & molecular medicine · 2025Article
- Parthanatos drives cognitive decline in repeated brain trauma: MSC-derived exosomes as a novel therapeutic strategy.Frontiers in pharmacology · 2025Article
- Poly ADP-Ribose Polymerase-1 inhibition by 3-aminobenzamide recuperates HEI-OC1 auditory hair cells from blast overpressure-induced cell death.Frontiers in cell and developmental biology · 2023Article
- Possible Action of Olaparib for Preventing Invasion of Oral Squamous Cell Carcinoma In Vitro and In Vivo.International journal of molecular sciences · 2022Article
- Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases.Cancers · 2022Review
- Depletion of PARP10 inhibits the growth and metastatic potential of oral squamous cell carcinoma.Frontiers in genetics · 2022Article
- Poly (ADP-ribose) polymerases as PET imaging targets for central nervous system diseases.Frontiers in medicine · 2022Review
- Emerging role of PARP-1 and PARthanatos in ischemic stroke.Journal of neurochemistry · 2022Review
- Poly(ADP-ribose) polymerase inhibition: past, present and future.Nature reviews. Drug discovery · 2020Review
- Review
- 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
- Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Combining PARP and DNA-PK Inhibitors With Irradiation Inhibits HPV-Negative Head and Neck Cancer Squamous Carcinoma Growth.Frontiers in genetics · 2020Article
- Review
- 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
- Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Cathepsin B inhibition ameliorates leukocyte-endothelial adhesion in the BTBR mouse model of autism.CNS neuroscience & therapeutics · 2019Article
- Breakdown of blood brain barrier as a mechanism of post-traumatic epilepsy.Neurobiology of disease · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBlood-brain barrier (BBB) dysfunction/disruption followed by leukocyte infiltration into the brain causes neuroinflammation and contributes to morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. The identification of pathways that decreases the inflammatory potential of leukocytes would prevent such injury. Poly(ADP-ribose) polymerase 1 (PARP) controls various genes via its interaction with myriad transcription factors. Selective PARP inhibitors have appeared lately as potent anti-inflammatory tools. Their effects are outside the recognized PARP functions in DNA repair and transcriptional regulation. In this study, we explored the idea that selective inhibition of PARP in leukocytes would diminish their engagement of the brain endothelium.
methodsCerebral vascular changes and leukocyte-endothelium interactions were surveyed by intravital videomicroscopy utilizing a novel in vivo model of localized aseptic meningitis when TNFα was introduced intracerebrally in wild-type (PARP
resultsPARP suppression in monocytes diminished their adhesion to and migration across BBB in vitro models and prevented barrier injury. In monocytes, PARP inactivation decreased conformational activation of integrins that plays a key role in their tissue infiltration. Such changes were mediated by suppression of activation of small Rho GTPases and cytoskeletal rearrangements in monocytes. In vitro observations were confirmed in vivo showing diminished leukocyte-endothelial interaction after selective PARP suppression in leukocytes accompanied by BBB protection. PARP knockout animals demonstrated a substantial diminution of inflammatory responses in brain microvasculature and a decrease in BBB permeability.
conclusionsThese results suggest PARP inhibition in leukocytes as a novel approach to BBB protection in the setting of endothelial dysfunction caused by inflammation-induced leukocyte engagement.
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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.