Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products

J Neurosurg. 2002 Feb;96(2):287-93. doi: 10.3171/jns.2002.96.2.0287.


Object: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bilirubin / adverse effects
  • Bilirubin / physiology
  • Brain / drug effects
  • Brain / physiopathology
  • Brain Edema / chemically induced
  • Brain Edema / etiology*
  • Brain Edema / physiopathology*
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / physiopathology*
  • Deferoxamine / pharmacology
  • Disease Models, Animal
  • Fibrin Fibrinogen Degradation Products / physiology*
  • Heme Oxygenase (Decyclizing) / adverse effects
  • Heme Oxygenase (Decyclizing) / antagonists & inhibitors
  • Heme Oxygenase (Decyclizing) / physiology
  • Heme Oxygenase-1
  • Hemin / adverse effects
  • Hemin / physiology
  • Hemoglobins / adverse effects*
  • Hemoglobins / drug effects
  • Hemoglobins / physiology*
  • Male
  • Metalloporphyrins / pharmacology
  • Protoporphyrins / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stereotaxic Techniques
  • Up-Regulation / physiology


  • Fibrin Fibrinogen Degradation Products
  • Hemoglobins
  • Metalloporphyrins
  • Protoporphyrins
  • tin protoporphyrin IX
  • Hemin
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Deferoxamine
  • Bilirubin