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A Novel PARP Inhibitor L-2286 in a Rat Model of Impact Acceleration Head Injury: An Immunohistochemical and Behavioral Study
- Source :
- International Journal of Molecular Sciences, Vol 11, Iss 4, Pp 1253-1268 (2010), International Journal of Molecular Sciences, International Journal of Molecular Sciences; Volume 11; Issue 4; Pages: 1253-1268
- Publication Year :
- 2010
- Publisher :
- MDPI AG, 2010.
-
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 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.
- Subjects :
- Male
Pharmacology
Anxiety
lcsh:Chemistry
Piperidines
Amyloid precursor protein
Enzyme Inhibitors
lcsh:QH301-705.5
Spectroscopy
biology
Behavior, Animal
traumatic brain injury
Head injury
General Medicine
Immunohistochemistry
Computer Science Applications
Infusions, Intraventricular
Neuroprotective Agents
Anesthesia
PARP inhibitor
Poly(ADP-ribose) Polymerases
PARP-inhibitor
Elevated plus maze
Traumatic brain injury
Poly(ADP-ribose) Polymerase Inhibitors
Neuroprotection
Catalysis
Article
Inorganic Chemistry
medicine
Animals
Physical and Theoretical Chemistry
Rats, Wistar
Molecular Biology
business.industry
Organic Chemistry
impact acceleration model
medicine.disease
Axons
Rats
Disease Models, Animal
lcsh:Biology (General)
lcsh:QD1-999
Brain Injuries
Corticospinal tract
biology.protein
Quinazolines
business
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 11
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....1c165934518cd7d249434be286ce2bb2