ArticleThe Journal of pharmacology and experimental therapeutics2005
Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways and secondary damage in experimental spinal cord trauma.
Article in The Journal of pharmacology and experimental therapeutics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 71 citations in OpenAlex.
- NADSpinal cord · 2026Review
- Targeting the PARP1-p53 Axis Could Mitigate Necrotic-Apoptotic Signaling and Secondary Neurodegeneration After Spinal Cord Injury.Molecular neurobiology · 2026Article
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- Oxidative DNA Damage in the Pathophysiology of Spinal Cord Injury: Seems Obvious, but Where Is the Evidence?Antioxidants (Basel, Switzerland) · 2022Review
- PARP-1-Associated Pathological Processes: Inhibition by Natural Polyphenols.International journal of molecular sciences · 2021Review
- PARP overactivation in neurological disorders.Molecular biology reports · 2021Review
- The Role of PARPs in Inflammation-and Metabolic-Related Diseases: Molecular Mechanisms and Beyond.Cells · 2019Review
- PKC, AKT and ERK1/2-Mediated Modulations of PARP1, NF-κB and PEA15 Activities Distinctly Regulate Regional Specific Astroglial Responses Following Status Epilepticus.Frontiers in molecular neuroscience · 2019Article
- Involvement of poly(ADP-ribose) polymerase-1 in development of spinal cord injury in Chinese individuals: a Chinese clinical study.Drug design, development and therapy · 2017Article
- Therapeutic applications of PARP inhibitors: anticancer therapy and beyond.Molecular aspects of medicine · 2013Review
- The potential of PARP inhibitors in neuro-oncology.CNS oncology · 2012Review
- Anti-inflammatory effect of oleuropein in experimental rat spinal cord trauma.Iranian Red Crescent medical journal · 2012Article
- Effects of 6(5H)-phenanthridinone, an inhibitor of poly(ADP-ribose)polymerase-1 activity (PARP-1), on locomotor networks of the rat isolated spinal cord.Cellular and molecular neurobiology · 2011Article
- Signaling mechanism of poly(ADP-ribose) polymerase-1 (PARP-1) in inflammatory diseases.The American journal of pathology · 2011Review
- Molecular Mechanisms Underlying Cell Death in Spinal Networks in Relation to Locomotor Activity After Acute Injury in vitro.Frontiers in cellular neuroscience · 2011Article
- Anti-inflammatory effect of the epigallocatechin gallate following spinal cord trauma in rat.Iranian biomedical journal · 2011Article
- Kainate-mediated excitotoxicity induces neuronal death in the rat spinal cord in vitro via a PARP-1 dependent cell death pathway (Parthanatos).Cellular and molecular neurobiology · 2010Article
- Olprinone attenuates the acute inflammatory response and apoptosis after spinal cord trauma in mice.PloS one · 2010Article
- Effect of poly (ADP-ribose) polymerase-1 inhibition on the proliferation of murine colon carcinoma CT26 cells.Pathology oncology research : POR · 2009Article
- Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos.Experimental neurology · 2009Review
Corrections and comments
- Expression of concern
- Expression of concern
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with stroke and neurotrauma. The aim of our study was to evaluate the therapeutic efficacy of in vivo inhibition of PARP in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration (measured as an increase in myeloperoxidase activity), and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated UTP end labeling coloration). Infiltration of spinal cord tissue with neutrophils was associated with a marked increase in immunoreactivity for poly(ADP-ribose) (PAR), index of PARP activation, in the spinal cord tissue. These inflammatory events were associated with the activation of nuclear factor-kappaB (NF-kappaB) at 4 h after spinal cord damage. Treatment of the mice with the PARP inhibitors 3-aminobenzamide (3-AB) or 5-aminoisoquinolinone (5-AIQ) significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score), 2) PAR formation, 3) neutrophil infiltration, and 4) apoptosis. Treatment with these PARP inhibitors also reduced DNA binding of NF-kappaB and inhibitory kappaB degradation. In a separate set of experiments, we have also demonstrated that PARP inhibitors significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with PARP inhibitors reduces the development of inflammation and tissue injury events associated with spinal cord trauma.
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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.