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Int. J. Mol. Sci. 2010, 11(4), 1253-1268;

A Novel PARP Inhibitor L-2286 in a Rat Model of Impact Acceleration Head Injury: An Immunohistochemical and Behavioral Study

Department of Neurosurgery, Medical Faculty, University of Pécs, 7623 Pécs, Hungary
Laboratoire de Pharmacologie de la Circulation Cérébrale, UPRES EA 2510, Université René Descartes, Paris, France
Department of BioChemistry, University of Pécs, 7624 Pécs, Hungary
Department of Experimental Zoology and Neurobiology, University of Pécs, 7624, Hungary
Author to whom correspondence should be addressed.
Received: 3 November 2009 / Revised: 11 March 2010 / Accepted: 22 March 2010 / Published: 26 March 2010
(This article belongs to the Special Issue Neuroprotective Strategies (special issue))
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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. View Full-Text
Keywords: PARP-inhibitor; impact acceleration model; traumatic brain injury PARP-inhibitor; impact acceleration model; traumatic brain injury

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Kövesdi, E.; Bukovics, P.; Besson, V.; Nyirádi, J.; Lückl, J.; Pál, J.; Sümegi, B.; Dóczi, T.; Hernádi, I.; Büki, A. A Novel PARP Inhibitor L-2286 in a Rat Model of Impact Acceleration Head Injury: An Immunohistochemical and Behavioral Study. Int. J. Mol. Sci. 2010, 11, 1253-1268.

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