title: Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage.
abstract: Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology*; D019190:Iron Overload / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D003676:Deferoxamine