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• Kövesdi, E
• Bukovics, P
• Besson, V
• Nyirádi, J
• Lückl, J
• Pál, J
• Sümegi, B
• Dóczi, T
• Hernádi, I
• Büki, A
• [+] on Google Scholar
• Kövesdi, E
• Bukovics, P
• Besson, V
• Nyirádi, J
• Lückl, J
• Pál, J
• Sümegi, B
• Dóczi, T
• Hernádi, I
• Büki, A
• [+] on PubMed
• Kövesdi, E
• Bukovics, P
• Besson, V
• Nyirádi, J
• Lückl, J
• Pál, J
• Sümegi, B
• Dóczi, T
• Hernádi, I
• Büki, A

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Int. J. Mol. Sci. 2010, 11(4), 1253-1268; doi:10.3390/ijms11041253

Article

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

Erzsébet Kövesdi ¹ , Péter Bukovics ¹ , Valérie Besson ² , József Nyirádi ¹ , János Lückl ¹ , József Pál ¹ , Balázs Sümegi ³ , Tamás Dóczi ¹ , István Hernádi ⁴  and András Büki ^1,*

¹ Department of Neurosurgery, Medical Faculty, University of Pécs, 7623 Pécs, Hungary ² Laboratoire de Pharmacologie de la Circulation Cérébrale, UPRES EA 2510, Université René Descartes, Paris, France ³ Department of BioChemistry, University of Pécs, 7624 Pécs, Hungary ⁴ Department of Experimental Zoology and Neurobiology, University of Pécs, 7624, Hungary

* Author to whom correspondence should be addressed.

Received: 3 November 2009; in revised form: 11 March 2010 / Accepted: 22 March 2010 / Published: 26 March 2010

(This article belongs to the Special Issue Neuroprotective Strategies)

Download PDF Full-Text [932 KB, uploaded 26 March 2010 10:46 CET]

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.

Keywords: PARP-inhibitor; impact acceleration model; traumatic brain injury

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