title: Role of iron in brain lipocalin 2 upregulation after intracerebral hemorrhage in rats.
abstract: Brain iron overload has a detrimental role in brain injury after intracerebral hemorrhage (ICH). Lipocalin 2 (LCN2), a siderophore-binding protein, is involved in cellular iron transport. The present study investigated changes in LCN2 expression after ICH and the role of iron in those changes. Male Sprague-Dawley rats had an intracaudate injection of autologous blood (ICH) or iron. Control rats received a needle insertion or saline injection. Some ICH animals were treated with either vehicle or deferoxamine, an iron chelator. Brain LCN2 expression was determined by Western blot analysis and immunohistochemistry. Real-time PCR was also used to confirm brain LCN2 mRNA expression. The number of LCN2 positive cells was markedly increased in the ipsilateral basal ganglia and cortex after ICH and most LCN2 positive cells were astrocytes. Western blots showed that brain LCN2 levels were higher at days 1, 3 and 7 in the ipsilateral hemisphere after ICH (70 to 80 fold higher than contralateral hemisphere or sham-operated rats at 3 days), and declined to lower levels at day 14. Iron, but not saline injection also caused brain LCN2 upregulation (a more than 100-fold increase). In addition, systemic treatment of deferoxamine reduced ICH-induced LCN2 upregulation (p<0.05). These results suggest that iron has a role in brain LCN2 upregulation following ICH. LCN2 upregulation after ICH may be part of the response to clear iron released from the hematoma during clot resolution.
authors: Deparment of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
authors: Ming
authors: M
authors: Dong
authors: Guohua
authors: G
authors: Xi
authors: Richard F
authors: RF
authors: Keep
authors: Ya
authors: Y
authors: Hua
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000473:pathology*; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D012333:RNA, Messenger; D007501:Iron; D010751:Phosphopyruvate Hydratase; D003676:Deferoxamine