title: Deferoxamine alleviates chronic hydrocephalus after intraventricular hemorrhage through iron chelation and Wnt1/Wnt3a inhibition.
abstract: Post-hemorrhagic chronic hydrocephalus (PHCH) is a common complication after intraventricular hemorrhage (IVH). The mechanism of PHCH is not fully understood, and its treatment is relatively difficult. In the present study, a rat model of PHCH was used to elucidate the role of iron in the pathogenesis of PHCH. The action of deferoxamine (DFX) in IVH-induced PHCH, the expression of brain ferritin, the concentration of iron in cerebrospinal fluid (CSF), and changes in Wnt1/Wnt3a gene expression were determined. Results indicate that iron plays an important role in the occurrence of hydrocephalus after IVH. The iron chelator, DFX, can decrease the concentrations of iron and ferritin after cerebral hemorrhage and can thereby decrease the incidence of hydrocephalus. In addition, after IVH, the gene expression of Wnt1 and Wnt3a was enhanced, with protein expression also upregulated; DFX was able to suppress both gene and protein expression of Wnt1 and Wnt3a in brain tissue. This indicates that iron may be the key stimulus that activates the Wnt signaling pathway and regulates subarachnoid fibrosis after cerebral hemorrhage, and that DFX may be a candidate for preventing PHCH in patients with IVH.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China.
authors.forename: Guoqi
authors.initials: G
authors.lastname: Gong
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, GaoTanYan Street, ShaPingBa, Chongqing 400038, China. Electronic address: fuafeng_111@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005293:Ferritins / Q000378:metabolism; D006849:Hydrocephalus / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007501:Iron / Q000134:cerebrospinal fluid; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D051155:Wnt1 Protein / Q000378:metabolism; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D060509:Wnt3A Protein; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine
keywords: Deferoxamine; Intraventricular hemorrhage; Iron chelation; Post-hemorrhagic chronic hydrocephalus; Wnt signaling pathway