Effects of deferoxamine on brain injury after transient focal cerebral ischemia in rats with hyperglycemia.
Hemorrhagic transformation (HT) is a major factor limiting the use of tissue plasminogen activator (tPA) for stroke patients. This study examined the role of deferoxamine (DFX) in brain injury and HT in a rat model of transient focal ischemia with hyperglycemia. Rats received an injection of 50% glucose (6 mL/kg, i.p.) 15 min before undergoing transient middle cerebral artery occlusion (tMCAO; 2 h occlusion) with reperfusion. Rats were treated with DFX (100 mg/ kg, i.m.) or vehicle immediately after tMCAO. Rats were killed at 4, 8 and 24 h later and used for brain edema, blood-brain barrier permeability, hemorrhage volume, hemoglobin content, and infarct volume measurements. Mortality rate was also evaluated. DFX treatment reduced mortality at 24 h (4% vs. 24% in the vehicle-treated group, p<0.05). DFX also reduced infarct volume (85.1+/-56.3 vs. 164.3+/-93.4 mm(3) in vehicle, p<0.05) and swelling in the basal ganglia (p<0.05) 24 h after tMCAO. The total hemorrhage volume in the ipsilateral hemisphere at 8 h post tMCAO was less in DFX-treated animals (p<0.05). However, blood-brain barrier permeability was same in DFX- and vehicle-treated groups. DFX attenuates death rate, hemorrhagic transformation, infarct volume, and brain swelling in a rat transient focal ischemia with hyperglycemia model, suggesting that DFX could be potential treatment to reduce the hemorrhagic transformation for stroke patients.
Xing
Yingqi
Y
Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Hua
Ya
Y
Keep
Richard F
RF
Xi
Guohua
G
D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001834:Body Water / Q000737:chemistry; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D001929:Brain Edema / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006943:Hyperglycemia / Q000150:complications / Q000401:mortality / Q000473:pathology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D020300:Intracranial Hemorrhages / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology
D006454:Hemoglobins; D003676:Deferoxamine