Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo

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 poorl...

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Autores principales:	Ma,Jiao, Yu,Dan, Tong,Yu, Mao,Meng
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2012
Materias:	excitotoxicity hypoxia-ischemia neuroserpin N-methyl-D-aspartic tissue-type plasminogen activator
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602012000400005
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spelling	oai:scielo:S0716-976020120004000052013-03-15Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivoMa,JiaoYu,DanTong,YuMao,Meng excitotoxicity hypoxia-ischemia neuroserpin N-methyl-D-aspartic tissue-type plasminogen activator 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.45 n.4 20122012-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602012000400005en10.4067/S0716-97602012000400005
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	excitotoxicity hypoxia-ischemia neuroserpin N-methyl-D-aspartic tissue-type plasminogen activator
spellingShingle	excitotoxicity hypoxia-ischemia neuroserpin N-methyl-D-aspartic tissue-type plasminogen activator Ma,Jiao Yu,Dan Tong,Yu Mao,Meng Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
description	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.
author	Ma,Jiao Yu,Dan Tong,Yu Mao,Meng
author_facet	Ma,Jiao Yu,Dan Tong,Yu Mao,Meng
author_sort	Ma,Jiao
title	Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
title_short	Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
title_full	Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
title_fullStr	Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
title_full_unstemmed	Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
title_sort	effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo
publisher	Sociedad de Biología de Chile
publishDate	2012
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602012000400005
work_keys_str_mv	AT majiao effectofneuroserpininaneonatalhypoxicischemicinjurymodelexvivo AT yudan effectofneuroserpininaneonatalhypoxicischemicinjurymodelexvivo AT tongyu effectofneuroserpininaneonatalhypoxicischemicinjurymodelexvivo AT maomeng effectofneuroserpininaneonatalhypoxicischemicinjurymodelexvivo
_version_	1718441492823932928

Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo

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