Biological signatures of brain damage associated with high serum ferritin levels in patients with acute ischemic stroke and thrombolytic treatment.
OBJECTIVE
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.
Millán
Mónica
M
Department of Neurosciences, Hospital Germans Trias i Pujol, Departament de Medicina, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain. mmillan.germanstrias@gencat.net
Sobrino
Tomás
T
Arenillas
Juan Francisco
JF
Rodríguez-Yáñez
Manuel
M
García
María
M
Nombela
Florentino
F
Castellanos
Mar
M
de la Ossa
Natalia Pérez
NP
Cuadras
Patricia
P
Serena
Joaquín
J
Castillo
José
J
Dávalos
Antoni
A
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood* / Q000209:etiology; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D015415:Biomarkers; D005293:Ferritins; D010959:Tissue Plasminogen Activator