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Thromb Haemost 2011; 105(03): 421-429
DOI: 10.1160/TH10-09-0621
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The natural tissue plasminogen activator inhibitor neuroserpin and acute ischaemic stroke outcome

Raquel Rodríguez-González   *
1   Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
,
Mónica Millán   *
2   Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
,
Tomás Sobrino
1   Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
,
Elena Miranda
3   University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK
,
David Brea
1   Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
,
Natalia Pérez de la Ossa
2   Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
,
Miguel Blanco
1   Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
,
Juan Pérez
4   Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Facultad de Ciencias, Málaga, Spain
,
Laura Dorado
2   Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
,
Mar Castellanos
5   Department of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain
,
David A. Lomas
3   University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK
,
Maria A. Moro
6   Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain
,
Antoni Dávalos
2   Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
,
José Castillo
1   Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
› Author Affiliations Financial support: This project has been partially supported by grants from the Spanish Ministry of Science and Innovation (CIT-090100–2007–42) and (PI081472); Xunta de Galicia: Consellería de Innovación, Industria e Comercio (PGIDIT06PXIB918316PR), and Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III) RETICS RENEVAS: (RD06/0026). R. Rodríguez-González and D. Brea are recipients of fellowships from Instituto de Salud Carlos III of the Spanish Ministry of Science and Innovation (Ayudas predoctorales de formación en investigación).
Further Information

Publication History

Received: 29 September 2010

Accepted after major revision: 25 November 2010

Publication Date:
27 November 2017 (online)

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Summary

Neuroserpin is a brain-derived natural inhibitor of tissue plasminogen activator (tPA) that has shown neuroprotective effects in animal models of brain ischaemia. Our aim was to investigate the association of neuroserpin levels in blood with functional outcome in patients with acute ischaemic stroke. Due to the potential effect of tPA treatment interfering on neuroserpin levels, we studied two different cohorts: 129 patients not treated with tPA and 80 patients treated with intravenous tPA within 3 hours (h) from symptoms onset. Neuroserpin levels were measured by ELISA. Good functional outcome at three months was defined as Rankin scale score ≤2. In the two cohorts, serum neuroserpin levels on admission were significantly higher than at 24 h, 72 h and in healthy subjects. In non tPA-treated patients, neuroserpin levels decrease at 24 h, but not levels at baseline, were associated with good outcome (for each quartile decrease, adjusted odds ratio [OR] 15.0; 95% confidence interval [CI], 3.5 to 66). In the tPA-treated cohort, high neuroserpin levels before tPA bolus had the stronger effect on favourable outcome (for each quartile, OR 13.5; 95%CI, 3.9 to 47). Furthermore, for each quartile in neuroserpin levels before tPA bolus there was a 80% (95%CI, 48 to 92) reduction in the probability of subsequent parenchymal haematoma. In summary, high serum neuroserpin levels before intravenous tPA and neuroserpin levels decrease at 24 h after ischaemic stroke, independently of tPA treatment, are associated with good functional outcome. These findings support the concept that neuroserpin might play an important role during cerebral ischaemia.

Keywords

Neuroserpin - outcome - stroke - tissue plasminogen activator

* R. Rodríguez- González and M. Millán contributed equally to this work.


 

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