Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
Biol. Res
;
45(4): 357-362, 2012. ilus
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Neuropeptides
/
Serpines
/
Activateur tissulaire du plasminogène
/
Neuroprotecteurs
/
Hypoxie-ischémie du cerveau
Type d'étude:
Etude d'étiologie
Limites du sujet:
Animaux
/
Grossesse
langue:
Anglais
Texte intégral:
Biol. Res
Thème du journal:
Biologie
Année:
2012
Type:
Article
/
descriptif de projet
Pays d'affiliation:
Chine
Institution/Pays d'affiliation:
Sichuan University/CN
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