Long-term effects of experimental intracerebral hemorrhage: the role of iron.
OBJECTIVE
Intracerebral hemorrhage (ICH) causes brain atrophy and neurological deficits. The mechanisms of brain atrophy after ICH are poorly understood, although recent evidence suggests that some ICH-induced brain injury results from the products of hemoglobin degradation, including iron. In this study the authors examine the role of iron in brain atrophy and neurological deficits following ICH.


METHODS
Male Sprague-Dawley rats received an infusion of either 100 microl autologous whole blood or saline into the right caudate. Hematoxylin and eosin staining was used for histological examination, and iron levels and ferritin immunoreactivities were also examined. Deferoxamine was used as an iron chelator. Over the duration of the experiment, the rats underwent behavioral testing (forelimb placing, forelimb use asymmetry, and corner turn tests). Brain atrophy in the caudate with prolonged neurological deficits occurred after ICH. Although partial functional recovery occurred with time, residual neurological deficits were still detectable at 3 months postprocedure. Iron accumulation and ferritin upregulation were present in the ipsilateral caudate. Deferoxamine reduced brain atrophy and improved behavioral outcomes, and it also reduced brain ferritin immunoreactivity.


CONCLUSIONS
An ICH results in an accumulation of iron in the brain that is not cleared within 3 months and that contributes to brain tissue loss and neurological deficits posthemorrhage. Iron chelation may be a useful therapy for patients with ICH.
Hua
Ya
Y
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
Nakamura
Takehiro
T
Keep
Richard F
RF
Wu
Jimin
J
Schallert
Timothy
T
Hoff
Julian T
JT
Xi
Guohua
G
D000818:Animals; D001284:Atrophy; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D003676:Deferoxamine / Q000494:pharmacology; D005293:Ferritins / Q000096:biosynthesis; D020300:Intracranial Hemorrhages / Q000150:complications*; D007501:Iron / Q000493:pharmacokinetics* / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000494:pharmacology; D015854:Up-Regulation
D017262:Siderophores; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine