Interleukin-1beta-induced brain injury in the neonatal rat can be ameliorated by alpha-phenyl-n-tert-butyl-nitrone.
Exp Neurol
; 220(1): 143-53, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19682987
ABSTRACT
To examine the possible role of inflammatory cytokines in mediating perinatal brain injury, we investigated effects of intracerebral injection of interleukin-1beta (IL-1beta) on brain injury in the neonatal rat and the mechanisms involved. Intracerebral administration of IL-1beta (1 microg/kg) resulted in acute brain injury, as indicated by enlargement of ventricles bilaterally, apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. IL-1beta also induced axonal and neuronal injury in the cerebral cortex as indicated by elevated expression of beta-amyloid precursor protein, short beaded axons and dendrites, and loss of tyrosine hydroxylase-positive neurons in the substantia nigra and the ventral tegmental areas. Administration of alpha-phenyl-n-tert-butyl-nitrone (PBN, 100 mg/kg i.p.) immediately after the IL-1beta injection protected the brain from IL-1beta-induced injury. Protection of PBN was linked with the attenuated oxidative stress induced by IL-1beta, as indicated by decreased elevation of 8-isoprostane content and by the reduced number of 4-hydroxynonenal or malondialdehyde or nitrotyrosine-positive cells following IL-1beta exposure. PBN also attenuated IL-1beta-stimulated inflammatory responses as indicated by the reduced activation of microglia. The finding that IL-1beta induced perinatal brain injury was very similar to that induced by lipopolysaccharide (LPS), as we previously reported and that PBN was capable to attenuate the injury induced by either LPS or IL-1beta suggests that IL-1beta may play a critical role in mediating brain injury associated with perinatal infection/inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Dano Encefálico Crônico
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Fármacos Neuroprotetores
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Óxidos N-Cíclicos
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Encefalite
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Interleucina-1beta
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Exp Neurol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos