Published Online
on November 13, 2003

A more recent version of this article appeared on December 1, 2003

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Submitted on August 15, 2003
Accepted on August 22, 2003

Iron and Iron-Handling Proteins in the Brain After Intracerebral Hemorrhage

Jimin Wu MD; Ya Hua MD; Richard F. Keep PhD; Takehiro Nakamura MD; Julian T. Hoff MD; and Guohua Xi MD^*

From the Departments of Neurosurgery (J.W., Y.H., R.F.K., T.N., J.T.H., G.X.) and Physiology (R.F.K.), University of Michigan, Ann Arbor.

^* To whom correspondence should be addressed. E-mail: guohuaxi{at}umich.edu.

Background and Purpose--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 µL 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.

Key words: cerebral hemorrhage • ferritin • iron • receptors, transferrin • transferrin

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