Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
Biol. Res
;
45(4): 357-362, 2012. ilus
Artigo
em Inglês
| LILACS
| ID: lil-668686
ABSTRACT
Hypoxia-ischemia (HI) occurring in immature brains stimulates the expression of tissue-type plasminogen activator (tPA). Neuroserpin is a selected inhibitor of tPA in the central nerves system. However, the role that neuroserpin plays and the possible mechanisms involved during neonatal HI are poorly defined. In this study, an oxygen-glucose deprivation and reoxygenation (OGD/R) model was generated with cultured rat cortical neurons mimicking neonatal HI injury ex vivo, and an acute neuronal excitatory injury was induced by exposure to a high concentration of N-methyl-D-aspartic acid (NMDA). Cells received either neuroserpin or MK-801, an antagonist of the NMDA receptor, during OGD/R, and were incubated with or without neuroserpin after NMDA exposure. Cell viability and morphology were detected by a Cell Counting Kit-8 and immunohistochemical staining, respectively. TPA expression and activity were also assessed. We found that MK-801 alleviated injuries induced by OGD/R, suggesting an excitatory damage involvement. Neuroserpin provided a dose-dependent neuroprotective effect in both OGD/R and acute excitatory injuries by inhibiting the activity of tPA, without affecting neuronal tPA expression. Neuroserpin protected neurons against OGD/R even after a delayed administration of 3h. Collectively, our data indicate that neuroserpin protects neurons against OGD/R. mainly by inhibiting tPA-mediated acute neuronal excitotoxicity.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Neuropeptídeos
/
Serpinas
/
Ativador de Plasminogênio Tecidual
/
Fármacos Neuroprotetores
/
Hipóxia-Isquemia Encefálica
Tipo de estudo:
Estudo de etiologia
Limite:
Animais
/
Gravidez
Idioma:
Inglês
Revista:
Biol. Res
Assunto da revista:
Biologia
Ano de publicação:
2012
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
China
Instituição/País de afiliação:
Sichuan University/CN
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