title: Iron overload, measured as serum ferritin, increases brain damage induced by focal ischemia and early reperfusion.
abstract: High levels of iron, measured as serum ferritin, are associated to a worse outcome after stroke. However, it is not known whether ischemic damage might increase ferritin levels as an acute phase protein or whether iron overload affects stroke outcome. The objectives are to study the effect of stroke on serum ferritin and the contribution of iron overload to ischemic damage. Swiss mice were fed with a standard diet or with a diet supplemented with 2.5% carbonyl iron to produce iron overload. Mice were submitted to permanent (by ligature and by in situ thromboembolic models) or transient focal ischemia (by ligature for 1 or 3h). Treatment with iron diet produced an increase in the basal levels of ferritin in all the groups. However, serum ferritin did not change after ischemia. Animals submitted to permanent ischemia had the same infarct volume in the groups studied. However, in mice submitted to transient ischemia followed by early (1h) but not late reperfusion (3h), iron overload increased ischemic damage and haemorrhagic transformation. Iron worsens ischemic damage induced by transient ischemia and early reperfusion. In addition, ferritin is a good indicator of body iron levels but not an acute phase protein after ischemia.
authors.affiliation: Unidad de Investigación Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: García-Yébenes
authors.forename: Mónica
authors.initials: M
authors.lastname: Sobrado
authors.forename: Ana
authors.initials: A
authors.lastname: Moraga
authors.forename: Juan G
authors.initials: JG
authors.lastname: Zarruk
authors.forename: Victor G
authors.initials: VG
authors.lastname: Romera
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Pradillo
authors.forename: Natalia
authors.initials: N
authors.lastname: Perez de la Ossa
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D015415:Biomarkers; D001929:Brain Edema / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000209:etiology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005293:Ferritins / Q000097:blood*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology* / Q000628:therapy; D058085:Iron Compounds / Q000633:toxicity; D019190:Iron Overload / Q000097:blood / Q000150:complications / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D011897:Random Allocation; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D058085:Iron Compounds; C515100:iron pentacarbonyl; D005293:Ferritins