Deferoxamine reduces brain swelling in a rat model of hippocampal intracerebral hemorrhage.
In this study, we examine the effects of deferoxamine on hemoglobin-induced brain swelling in a newly developed hippocampal model of intracerebral hemorrhage (ICH). There were 2 parts to the experiments in this study. In the first part, male Sprague-Dawley rats received a 10-microL infusion of either packed red blood cells (RBC), lysed RBC, hemoglobin, ferrous iron, or saline, into the hippocampus. In the second part, rats received a 10-microL infusion of hemoglobin and then were treated with either deferoxamine (100 mg/kg, intraperitoneally, given immediately after hemoglobin injection, then every 12h for 24h) or vehicle. Rats were then killed to obtain hippocampus size and DNA damage measurements. We found that lysed RBC induced marked brain swelling in the hippocampus. Compared to saline, hemoglobin or iron injection caused swelling. Systemic use of deferoxamine reduced hemoglobin-induced brain swelling (6.14 +/- 0.45 vs. 7.11 +/- 0.58 mm2 in the vehicle group, p < 0.05). In addition, deferoxamine reduced hemoglobin-induced DNA damage. These results indicate that iron has a key role in hemoglobin-induced brain swelling. Deferoxamine may be a useful treatment for ICH patients.
Song
S
S
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Hua
Y
Y
Keep
R F
RF
He
Y
Y
Wang
J
J
Wu
J
J
Xi
G
G
D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D016923:Cell Death; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007839:Functional Laterality; D006454:Hemoglobins / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D020287:In Situ Nick-End Labeling / Q000379:methods; D007501:Iron / Q000008:administration & dosage; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000627:therapeutic use*
D006454:Hemoglobins; D017262:Siderophores; D007501:Iron; D003676:Deferoxamine