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

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

    Research output: Contribution to journalArticleResearchpeer-review

    18 Citations (Scopus)

    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. © 2008 - IOS Press and the authors. All rights reserved.
    Original languageEnglish
    Pages (from-to)181-188
    JournalDisease Markers
    Volume25
    Issue number3
    DOIs
    Publication statusPublished - 1 Jan 2008

    Keywords

    • Biomarkers
    • Blood-brain-barrier disruption
    • Excitotoxicity
    • Ferritin
    • Inflammation
    • Iron stores
    • Thrombolysis

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