title: Effect of Gender on Iron-induced Brain Injury in Low Aerobic Capacity Rats.
abstract: Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Low aerobic capacity is a risk factor for cardiovascular disease and our previous study demonstrated that ICH-induced brain injury is enhanced in rats with low aerobic capacity (low capacity runners; LCRs). We have found that ICH-induced injury is less in female rats compared with that in males. In the present study, we examined the effects of gender on iron-induced brain injury in rats with low aerobic capacity. Adult male and female LCR rats had an intracaudate injection of FeCl2 (50 μl 0.5 mM). T2 Magnetic resonance imaging was carried out at 24 h to determine brain swelling and T2 brain lesion volume. Albumin leakage, an indicator of blood-brain barrier (BBB) disruption, and heme oxygenase-1 (HO-1, a stress marker) levels were determined. Male LCR rats had more severe hemisphere swelling (difference of ipsilateral to contralateral hemisphere volume: 16.6 ± 4.1 vs 11.1 ± 2.6 % in females, p < 0.05) and larger T2 lesion volumes (120 ± 28 vs 87 ± 27 mm(3) in females, p < 0.05) after iron injection. Iron also resulted in more severe BBB disruption in the ipsilateral hemisphere of males (albumin levels: 7,717 ± 1,502 pixels in males vs 5,287 ± 1,342 pixels in females; p < 0.05). The immunoreactivity of HO-1 was also significantly higher in males than females (HO-1/β-actin: 1.31 ± 0.44 vs 1.03 ± 0.05, p < 0.05). Female LCR rats had less iron-induced brain swelling, smaller lesion volumes, and reduced BBB disruption and HO-1 upregulation compared with male LCR rats. This may contribute to the reduced ICH-induced brain injury found in females.
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Hanjian
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA. yahua@umich.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D001929:Brain Edema / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D001930:Brain Injuries / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity*; D017079:Exercise Tolerance; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D058085:Iron Compounds / Q000633:toxicity*; D008279:Magnetic Resonance Imaging; D008297:Male; D010805:Physical Conditioning, Animal; D051381:Rats; D012737:Sex Factors
chemical_list: D002712:Chlorides; D058085:Iron Compounds; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Blood-brain barrier; Heme oxygenase-1; Intracerebral hemorrhage; Iron