Biological signatures of brain damage associated with high serum ferritin levels in patients with acute ischemic stroke and thrombolytic treatment

Article type: Research Article

Authors: Millán, Mónica | Sobrino, Tomás | Arenillas, Juan Francisco | Rodríguez-Yáñez, Manuel | García, María | Nombela, Florentino | Castellanos, Mar | de la Ossa, Natalia Pérez | Cuadras, Patricia | Serena, Joaquín | Castillo, José | Dávalos, Antoni

Affiliations: Department of Neurosciences, Hospital Germans Trias i Pujol, Departament de Medicina, Universitat Autònoma de Barcelona, Spain | Department of Neurology, Clinical Neuroscience Research Laboratory, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Spain | Unit of Bioestatistics, Hospital Doctor Josep Trueta, Girona, Spain | Department of Neurology, Hospital de la Princesa, Madrid, Spain | Department of Neurology, Hospital Doctor Josep Trueta, Girona, Spain | Department of Radiology, Hospital Germans Trias i Pujol, Departament de Medicina, Universitat Autònoma de Barcelona, Spain

Note: [] Corresponding author: Mónica Millán, MD, Stroke Unit. Department of Neurosciences, Hospital Germans Trias i Pujol, Departament de Medicina, Universitat Autònoma de Barcelona, 08916 Badalona, Barcelona, Spain. Fax: 93 497 8742; E-mail: [email protected]

Abstract: Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p < 0.001) levels at baseline, and with glutamate (r = 0.57, p < 0.001), interleukin-6 (r = 0.49, p < 0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research.

Keywords: Iron stores, thrombolysis, ferritin, biomarkers, excitotoxicity, blood-brain-barrier disruption, inflammation

Journal: Disease Markers, vol. 25, no. 3, pp. 181-188, 2008