A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury: An immunohistochemical and behavioral study

Erzsébet Kövesdi, Péter Bukovics, Valérie Besson, József Nyirádi, János Lückl, József Pál, Balázs Sümegi, Tamás Dóczi, István Hernádi, András Büki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We examined the neuro/axono-protective potential of a novel poly (ADP-ribose) polymerase (PARP) inhibitor L-2286 in a rat impact acceleration brain injury model. Male Wistar rats (n = 70) weighing 300-350 grams were used to determine the most effective intracerebroventricular (i.c.v.) dose of L-2286 administered 30 min after injury, and to test the neuroprotective effect at two time points (immediately, and 30 min after injury). The neuroprotective effect of L-2286 was tested using immunohistochemical (amyloid precursor protein and mid-sized mouse anti-neurofilament clone RMO-14.9 antibody) and behavioral tests (beam-balance, open-field and elevated plus maze). At both time-points, a 100 μg/rat dose of i.c.v. L-2286 significantly (p < 0.05) reduced the density of damaged axons in the corticospinal tract and medial longitudinal fascicle compared to controls. In the behavioral tests, treatment 30 min post-injury improved motor function, while the level of anxiety was reduced in both treatment protocols.

Original languageEnglish
Pages (from-to)1253-1268
Number of pages16
JournalInternational journal of molecular sciences
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2010

Keywords

  • Impact acceleration model
  • PARP-inhibitor
  • Traumatic brain injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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