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The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo.
Mol Cell Neurosci. 2005 Dec; 30(4):552-8.MC

Abstract

Considering its brain-specific expression, neuroserpin (NS), a potent inhibitor of tissue-type plasminogen activator (tPA), might be a good therapeutic target to limit the pro-excitotoxic effects of tPA within the cerebral parenchyma, without affecting the benefit from thrombolysis in stroke patients. Here, we aimed at determining the mechanisms of action responsible for the previously reported neuroprotective activity of NS in rodent experimental cerebral ischemia. First, we show in vivo that exogenous NS protects the cortex and the striatum against NMDA-induced injury. Then, the cellular mechanisms of this neuroprotection were investigated in primary cultures of cortical neurons. We show that NS fails to prevent serum deprivation-induced apoptotic neuronal death, while it selectively prevents NMDA- but not AMPA-induced excitotoxicity. This beneficial effect is associated to a decrease in NMDA receptor-mediated intracellular calcium influx. Altogether, these data suggest that an overexpression of neuroserpin in the brain parenchyma might limit the deleterious effect of tPA on NMDA receptor-mediated neuronal death, which occurs following experimental ischemia.

Authors+Show Affiliations

INSERM-Avenir, tPA in the working brain, GIP CYCERON, Université de Caen, GIP Cyceron-Bd Henri Becquerel, 14074 Caen Cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16209928

Citation

Lebeurrier, Nathalie, et al. "The Brain-specific Tissue-type Plasminogen Activator Inhibitor, Neuroserpin, Protects Neurons Against Excitotoxicity Both in Vitro and in Vivo." Molecular and Cellular Neurosciences, vol. 30, no. 4, 2005, pp. 552-8.
Lebeurrier N, Liot G, Lopez-Atalaya JP, et al. The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo. Mol Cell Neurosci. 2005;30(4):552-8.
Lebeurrier, N., Liot, G., Lopez-Atalaya, J. P., Orset, C., Fernandez-Monreal, M., Sonderegger, P., Ali, C., & Vivien, D. (2005). The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo. Molecular and Cellular Neurosciences, 30(4), 552-8.
Lebeurrier N, et al. The Brain-specific Tissue-type Plasminogen Activator Inhibitor, Neuroserpin, Protects Neurons Against Excitotoxicity Both in Vitro and in Vivo. Mol Cell Neurosci. 2005;30(4):552-8. PubMed PMID: 16209928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo. AU - Lebeurrier,Nathalie, AU - Liot,Géraldine, AU - Lopez-Atalaya,José P, AU - Orset,Cyrille, AU - Fernandez-Monreal,Monica, AU - Sonderegger,Peter, AU - Ali,Carine, AU - Vivien,Denis, Y1 - 2005/10/04/ PY - 2005/06/08/received PY - 2005/08/25/revised PY - 2005/09/02/accepted PY - 2005/10/8/pubmed PY - 2006/5/2/medline PY - 2005/10/8/entrez SP - 552 EP - 8 JF - Molecular and cellular neurosciences JO - Mol Cell Neurosci VL - 30 IS - 4 N2 - Considering its brain-specific expression, neuroserpin (NS), a potent inhibitor of tissue-type plasminogen activator (tPA), might be a good therapeutic target to limit the pro-excitotoxic effects of tPA within the cerebral parenchyma, without affecting the benefit from thrombolysis in stroke patients. Here, we aimed at determining the mechanisms of action responsible for the previously reported neuroprotective activity of NS in rodent experimental cerebral ischemia. First, we show in vivo that exogenous NS protects the cortex and the striatum against NMDA-induced injury. Then, the cellular mechanisms of this neuroprotection were investigated in primary cultures of cortical neurons. We show that NS fails to prevent serum deprivation-induced apoptotic neuronal death, while it selectively prevents NMDA- but not AMPA-induced excitotoxicity. This beneficial effect is associated to a decrease in NMDA receptor-mediated intracellular calcium influx. Altogether, these data suggest that an overexpression of neuroserpin in the brain parenchyma might limit the deleterious effect of tPA on NMDA receptor-mediated neuronal death, which occurs following experimental ischemia. SN - 1044-7431 UR - https://www.unboundmedicine.com/medline/citation/16209928/The_brain_specific_tissue_type_plasminogen_activator_inhibitor_neuroserpin_protects_neurons_against_excitotoxicity_both_in_vitro_and_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-7431(05)00221-6 DB - PRIME DP - Unbound Medicine ER -