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, J. Pál, B. Sümegi, T. Dóczi, I. Hernádi, A. 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 2010

Fingerprint

2-((2-piperidin-1-ylethyl)thio)quinazolin-4(3H)-one
impact acceleration
Administrative data processing
ribose
adenosine diphosphate
Craniocerebral Trauma
inhibitors
rats
Rats
Neuroprotective Agents
Brain models
anxiety
brain damage
axons
dosage
Wounds and Injuries
Amyloid beta-Protein Precursor
Weighing
antibodies
Antibodies

Keywords

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

ASJC Scopus subject areas

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

Cite this

A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury : An immunohistochemical and behavioral study. / Kövesdi, Erzsébet; Bukovics, Péter; Besson, Valérie; Nyirádi, József; Lückl, János; Pál, J.; Sümegi, B.; Dóczi, T.; Hernádi, I.; Büki, A.

In: International Journal of Molecular Sciences, Vol. 11, No. 4, 04.2010, p. 1253-1268.

Research output: Contribution to journalArticle

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