A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury: an immunohistochemical and behavioral study.
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 microg/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.
Kövesdi
Erzsébet
E
Department of Neurosurgery, University of Pécs, Hungary. Erzsebert.Kovesdi.CTR@usuhs.mil
Bukovics
Péter
P
Besson
Valérie
V
Nyirádi
József
J
Lückl
János
J
Pál
József
J
Sümegi
Balázs
B
Dóczi
Tamás
T
Hernádi
István
I
Büki
András
A
D000818:Animals; D001007:Anxiety / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007150:Immunohistochemistry; D057967:Infusions, Intraventricular; D008297:Male; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C505456:2-((2-piperidin-1-ylethyl)thio)quinazolin-4(3H)-one; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011799:Quinazolines; D011065:Poly(ADP-ribose) Polymerases