title: The natural tissue plasminogen activator inhibitor neuroserpin and acute ischaemic stroke outcome.
abstract: 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.
authors.affiliation: Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-González
authors.forename: Mónica
authors.initials: M
authors.lastname: Millán
authors.forename: Tomás
authors.initials: T
authors.lastname: Sobrino
authors.forename: Elena
authors.initials: E
authors.lastname: Miranda
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.forename: Natalia Pérez
authors.initials: NP
authors.lastname: de la Ossa
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanco
authors.forename: Juan
authors.initials: J
authors.lastname: Perez
authors.forename: Laura
authors.initials: L
authors.lastname: Dorado
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Maria A
authors.initials: MA
authors.lastname: Moro
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.forename: José
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000473:pathology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007511:Ischemia; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D015843:Serpins / Q000378:metabolism / Q000494:pharmacology*; D020521:Stroke / Q000378:metabolism*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors*; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods; D000097522:Neuroserpin
chemical_list: D009479:Neuropeptides; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin