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Disease Markers
Volume 25, Issue 3, Pages 181-188

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

Mónica Millán,1 Tomás Sobrino,2 Juan Francisco Arenillas,1 Manuel Rodríguez-Yáñez,2 María García,3 Florentino Nombela,4 Mar Castellanos,5 Natalia Pérez de la Ossa,1 Patricia Cuadras,6 Joaquín Serena,5 José Castillo,2 and Antoni Dávalos1

1Department of Neurosciences, Hospital Germans Trias i Pujol, Departament de Medicina, Universitat Autònoma de Barcelona, Spain
2Department of Neurology, Clinical Neuroscience Research Laboratory, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Spain
3Unit of Bioestatistics, Hospital Doctor Josep Trueta, Girona, Spain
4Department of Neurology, Hospital de la Princesa, Madrid, Spain
5Department of Neurology, Hospital Doctor Josep Trueta, Girona, Spain
6Department of Radiology, Hospital Germans Trias i Pujol, Departament de Medicina, Universitat Autònoma de Barcelona, Spain

Received 8 December 2008; Accepted 8 December 2008

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.