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Int J Mol Sci ; 11(4): 1253-68, 2010 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-20480019

RESUMEN

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.


Asunto(s)
Conducta Animal/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Fármacos Neuroprotectores/farmacología , Piperidinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Quinazolinas/farmacología , Animales , Ansiedad/patología , Axones/metabolismo , Axones/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/química , Inmunohistoquímica , Infusiones Intraventriculares , Masculino , Fármacos Neuroprotectores/química , Piperidinas/química , Poli(ADP-Ribosa) Polimerasas/metabolismo , Quinazolinas/química , Ratas , Ratas Wistar
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