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

Raquel Rodríguez-González; Mónica Millán; Tomás Sobrino; Elena Miranda; David Brea; Natalia Pérez de la Ossa; Miguel Blanco; Juan Pérez; Laura Dorado; Mar Castellanos; David A. Lomas; Maria A. Moro; Antoni Dávalos; José Castillo

doi:10.1160/TH10-09-0621

Thrombosis and Haemostasis, Table of Contents

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

Authors

Raquel Rodríguez-González^*

¹Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Mónica Millán^*

²Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
Tomás Sobrino

¹Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Elena Miranda

³University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK
David Brea

¹Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Natalia Pérez de la Ossa

²Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
Miguel Blanco

¹Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Juan Pérez

⁴Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Facultad de Ciencias, Málaga, Spain
Laura Dorado

²Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
Mar Castellanos

⁵Department of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain
David A. Lomas

³University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK
Maria A. Moro

⁶Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain
Antoni Dávalos

²Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
José Castillo

¹Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain

Abstract

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

Full Text

References

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