RESUMO
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.
Assuntos
Ferritinas/sangue , Infarto da Artéria Cerebral Média/patologia , Sobrecarga de Ferro/patologia , Traumatismo por Reperfusão/patologia , Proteínas de Fase Aguda , Animais , Biomarcadores , Edema Encefálico/etiologia , Hemorragia Cerebral/etiologia , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Modelos Animais de Doenças , Progressão da Doença , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/terapia , Compostos de Ferro/toxicidade , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/terapia , Masculino , Camundongos , Distribuição Aleatória , Traumatismo por Reperfusão/complicações , Resultado do TratamentoRESUMO
Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons such as posttranslational modification of proteins or expression of new proteins via a signal transduction system to the nucleus. Secondly, a stress response and synthesis of stress proteins (heat shock proteins) may be activated. These mechanisms are mediated by chaperones. The objective of ischemic preconditioning research is to identify the underlying endogenous protective cellular receptors and signaling cascades, with the long-term goal of allowing therapeutic augmentation of the endogenous protective mechanisms in cerebral ischemia and possibly development of new neuroprotective strategies for ischemic stroke treatment.