title: Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products.
abstract: OBJECTIVE
  The mechanisms involved in brain edema formation following intracerebral hemorrhage (ICH) have not been fully elucidated. The authors have found that red blood cell lysis plays an important role in edema development after ICH. In the present study, they sought to determine whether degradation products of hemoglobin cause brain edema.
  
  
  METHODS
  Hemoglobin, hemin, bilirubin, or FeCl2 were infused with stereotactic guidance into the right basal ganglia of Sprague-Dawley rats. The animals were killed 24 hours later to determine brain water and ion contents. Western blot analysis and immunohistochemistry were applied for heme oxygenase-1 (HO-1) measurement. The effects of an HO inhibitor, tin-protoporphyrin (SnPP), and the iron chelator deferoxamine, on hemoglobin-induced brain edema were also examined. Intracerebral infusion of hemoglobin, hemin, bilirubin, or FeCl2 caused an increase in brain water content at 24 hours. The HO-1 was upregulated after hemoglobin infusion and HO inhibition by SnPP-attenuated hemoglobin-induced edema. Brain edema induced by hemoglobin was also attenuated by the intraperitoneal injection of 500 mg/kg deferoxamine.
  
  
  CONCLUSIONS
  Hemoglobin causes brain edema, at least in part, through its degradation products. Limiting hemoglobin degradation coupled with the use of iron chelators may be a novel therapeutic approach to limit brain edema after ICH.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor 48109-0532, USA.
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Huang
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.forename: Andrei
authors.initials: A
authors.lastname: Nemoianu
authors.forename: Julian T
authors.initials: JT
authors.lastname: Hoff
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000009:adverse effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001929:Brain Edema / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000503:physiopathology*; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000502:physiology; D051547:Heme Oxygenase-1; D006427:Hemin / Q000009:adverse effects / Q000502:physiology; D006454:Hemoglobins / Q000009:adverse effects* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D015854:Up-Regulation / Q000502:physiology
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D006427:Hemin; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D003676:Deferoxamine; D001663:Bilirubin