Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat

Valérie C. Besson, Zsuzsanna Zsengellér, Michel Plotkine, Csaba Szabo, Catherine Marchand-Verrecchia

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Traumatic brain injury produces peroxynitrite, a powerful oxidant which triggers DNA strand breaks, leading to the activation of poly(ADP-ribose) polymerase-1 (PARP-1). We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target. In order to confirm this hypothesis, we investigated the effects of PJ34 and INO-1001, two PARP inhibitors from structural classes other than benzamide, on the post-traumatic consequences. Pre- and post-treatments with PJ34 (30 mg/kg/day) and INO-1001 (10 mg/kg/day) decrease the neurological deficit at 3 days post-injury and this deficit is still reduced at 7 days. These neurological recovery-promoting effects are associated with the inhibition of PARP-1 activation caused by trauma, as demonstrated by abolishment of immunostaining of poly(ADP-ribose). Thus, the present work strengthens strongly the concept that PARP-1 inhibition may be a suitable approach for the treatment of brain trauma.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalBrain Research
Volume1041
Issue number2
DOIs
StatePublished - Apr 18 2005
Externally publishedYes

Fingerprint

Water
Poly Adenosine Diphosphate Ribose
Percussion
Peroxynitrous Acid
DNA Breaks
Wounds and Injuries
Oxidants
Poly (ADP-Ribose) Polymerase-1
Traumatic Brain Injury
Poly(ADP-ribose) Polymerase Inhibitors
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
INO 1001
Therapeutics
3-aminobenzamide
rat Parp1 protein
benzamide

Keywords

  • Inhibitors
  • Neurological deficit
  • Neuroprotection
  • Poly(ADP-ribose) polymerase
  • Rat
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat. / Besson, Valérie C.; Zsengellér, Zsuzsanna; Plotkine, Michel; Szabo, Csaba; Marchand-Verrecchia, Catherine.

In: Brain Research, Vol. 1041, No. 2, 18.04.2005, p. 149-156.

Research output: Contribution to journalArticle

Besson, Valérie C. ; Zsengellér, Zsuzsanna ; Plotkine, Michel ; Szabo, Csaba ; Marchand-Verrecchia, Catherine. / Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat. In: Brain Research. 2005 ; Vol. 1041, No. 2. pp. 149-156.
@article{6fa9b1efc19d4ba6bcbebe6075100a53,
title = "Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat",
abstract = "Traumatic brain injury produces peroxynitrite, a powerful oxidant which triggers DNA strand breaks, leading to the activation of poly(ADP-ribose) polymerase-1 (PARP-1). We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target. In order to confirm this hypothesis, we investigated the effects of PJ34 and INO-1001, two PARP inhibitors from structural classes other than benzamide, on the post-traumatic consequences. Pre- and post-treatments with PJ34 (30 mg/kg/day) and INO-1001 (10 mg/kg/day) decrease the neurological deficit at 3 days post-injury and this deficit is still reduced at 7 days. These neurological recovery-promoting effects are associated with the inhibition of PARP-1 activation caused by trauma, as demonstrated by abolishment of immunostaining of poly(ADP-ribose). Thus, the present work strengthens strongly the concept that PARP-1 inhibition may be a suitable approach for the treatment of brain trauma.",
keywords = "Inhibitors, Neurological deficit, Neuroprotection, Poly(ADP-ribose) polymerase, Rat, Traumatic brain injury",
author = "Besson, {Val{\'e}rie C.} and Zsuzsanna Zsengell{\'e}r and Michel Plotkine and Csaba Szabo and Catherine Marchand-Verrecchia",
year = "2005",
month = "4",
day = "18",
doi = "10.1016/j.brainres.2005.01.096",
language = "English (US)",
volume = "1041",
pages = "149--156",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat

AU - Besson, Valérie C.

AU - Zsengellér, Zsuzsanna

AU - Plotkine, Michel

AU - Szabo, Csaba

AU - Marchand-Verrecchia, Catherine

PY - 2005/4/18

Y1 - 2005/4/18

N2 - Traumatic brain injury produces peroxynitrite, a powerful oxidant which triggers DNA strand breaks, leading to the activation of poly(ADP-ribose) polymerase-1 (PARP-1). We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target. In order to confirm this hypothesis, we investigated the effects of PJ34 and INO-1001, two PARP inhibitors from structural classes other than benzamide, on the post-traumatic consequences. Pre- and post-treatments with PJ34 (30 mg/kg/day) and INO-1001 (10 mg/kg/day) decrease the neurological deficit at 3 days post-injury and this deficit is still reduced at 7 days. These neurological recovery-promoting effects are associated with the inhibition of PARP-1 activation caused by trauma, as demonstrated by abolishment of immunostaining of poly(ADP-ribose). Thus, the present work strengthens strongly the concept that PARP-1 inhibition may be a suitable approach for the treatment of brain trauma.

AB - Traumatic brain injury produces peroxynitrite, a powerful oxidant which triggers DNA strand breaks, leading to the activation of poly(ADP-ribose) polymerase-1 (PARP-1). We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target. In order to confirm this hypothesis, we investigated the effects of PJ34 and INO-1001, two PARP inhibitors from structural classes other than benzamide, on the post-traumatic consequences. Pre- and post-treatments with PJ34 (30 mg/kg/day) and INO-1001 (10 mg/kg/day) decrease the neurological deficit at 3 days post-injury and this deficit is still reduced at 7 days. These neurological recovery-promoting effects are associated with the inhibition of PARP-1 activation caused by trauma, as demonstrated by abolishment of immunostaining of poly(ADP-ribose). Thus, the present work strengthens strongly the concept that PARP-1 inhibition may be a suitable approach for the treatment of brain trauma.

KW - Inhibitors

KW - Neurological deficit

KW - Neuroprotection

KW - Poly(ADP-ribose) polymerase

KW - Rat

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=17044383375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17044383375&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2005.01.096

DO - 10.1016/j.brainres.2005.01.096

M3 - Article

VL - 1041

SP - 149

EP - 156

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -