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Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
Ma, Jiao; Yu, Dan; Tong, Yu; Mao, Meng.
  • Ma, Jiao; Sichuan University. West China Second University Hospital. Department of Pediatrics. Chengdu. CN
  • Yu, Dan; Sichuan University. West China Second University Hospital. Department of Pediatrics. Chengdu. CN
  • Tong, Yu; Sichuan University. West China Second University Hospital. Department of Pediatrics. Chengdu. CN
  • Mao, Meng; Sichuan University. West China Second University Hospital. Department of Pediatrics. Chengdu. CN
Biol. Res ; 45(4): 357-362, 2012. ilus
Article in English | 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.
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Full text: Available Index: LILACS (Americas) Main subject: Neuropeptides / Serpins / Tissue Plasminogen Activator / Neuroprotective Agents / Hypoxia-Ischemia, Brain Type of study: Etiology study Limits: Animals / Pregnancy Language: English Journal: Biol. Res Journal subject: Biology Year: 2012 Type: Article / Project document Affiliation country: China Institution/Affiliation country: Sichuan University/CN

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Full text: Available Index: LILACS (Americas) Main subject: Neuropeptides / Serpins / Tissue Plasminogen Activator / Neuroprotective Agents / Hypoxia-Ischemia, Brain Type of study: Etiology study Limits: Animals / Pregnancy Language: English Journal: Biol. Res Journal subject: Biology Year: 2012 Type: Article / Project document Affiliation country: China Institution/Affiliation country: Sichuan University/CN