Iron and iron-handling proteins in the brain after intracerebral hemorrhage.
OBJECTIVE
Evidence indicates that brain injury after intracerebral hemorrhage (ICH) is due in part to the release of iron from hemoglobin. Therefore, we examined whether such iron is cleared from the brain and the effects of ICH on proteins that may alter iron release or handling: brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin.


METHODS
Male Sprague-Dawley rats received an infusion of 100 microL autologous whole blood into the right basal ganglia and were killed 1, 3, 7, 14, or 28 days later. Enhanced Perl's reaction was used for iron staining, and brain nonheme iron content was determined. Brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin were examined by Western blot analysis and immunohistochemistry. Immunofluorescent double labeling was performed to identify which cell types express ferritin.


RESULTS
ICH upregulated heme oxygenase-1 levels and resulted in iron overload in the brain. A marked increase in brain nonheme iron was not cleared within 4 weeks. Brain transferrin and transferrin receptor levels were also increased. In addition, an upregulation of ICH on ferritin was of very long duration.


CONCLUSIONS
The iron overload and upregulation of iron-handling proteins, including transferrin, transferrin receptor, and ferritin, in the brain after ICH suggest that iron could be a target for ICH therapy.
Wu
Jimin
J
Department of Neurosurgery, University of Michigan, Ann Arbor 48109-0532, USA.
Hua
Ya
Y
Keep
Richard F
RF
Nakamura
Takehiro
T
Hoff
Julian T
JT
Xi
Guohua
G
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005293:Ferritins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D015854:Up-Regulation
D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1