2,4-Dinitrophenol blocks neurodegeneration and preserves sciatic nerve function after trauma.
J Neurotrauma
; 27(5): 829-41, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20143955
Preventing the harm caused by nerve degeneration is a major challenge in neurodegenerative diseases and in various forms of trauma to the nervous system. The aim of the current work was to investigate the effects of systemic administration of 2,4-dinitrophenol (DNP), a compound with newly recognized neuroprotective properties, on sciatic-nerve degeneration following a crush injury. Sciatic-nerve injury was induced by unilateral application of an aneurysm clip. Four groups of mice were used: uninjured, injured treated with vehicle (PBS), injured treated with two intraperitoneal doses of DNP (0.06 mg DNP/kg every 24 h), and injured treated with four doses of DNP (every 12 h). Animals were sacrificed 48 h post injury and both injured and uninjured (contralateral) sciatic nerves were processed for light and electron microscopy. Morphometric, ultrastructural, and immunohistochemical analysis of injured nerves established that DNP prevented axonal degeneration, blocked cytoskeletal disintegration, and preserved the immunoreactivity of amyloid precursor protein (APP) and Neuregulin 1 (Nrg1), proteins implicated in neuronal survival and myelination. Functional tests revealed preservation of limb function following injury in DNP-treated animals. Results indicate that DNP prevents nerve degeneration and suggest that it may be a useful small-molecule adjuvant in the development of novel therapeutic approaches in nerve injury.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Degeneração Walleriana
/
Fármacos Neuroprotetores
/
2,4-Dinitrofenol
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Recuperação de Função Fisiológica
/
Neuropatia Ciática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurotrauma
Assunto da revista:
NEUROLOGIA
/
TRAUMATOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos