title: Decorin alleviated chronic hydrocephalus via inhibiting TGF-β1/Smad/CTGF pathway after subarachnoid hemorrhage in rats.
abstract: Chronic hydrocephalus is one of the severe complications after subarachnoid hemorrhage (SAH). However, there is no efficient treatment for the prevention of chronic hydrocephalus, partially due to poor understanding of underlying pathogenesis, subarachnoid fibrosis. Transforming growth factor-β1(TGF-β1) is a potent fibrogenic factor implicated in wide range of fibrotic diseases. To investigate whether decorin, a natural antagonist for TGF-β1, protects against subarachnoid fibrosis and chronic hydrocephalus after SAH, two-hemorrhage-injection SAH model was conducted in 6-week-old rats. Recombinant human decorin(rhDecorin) (30ug/2ul) was administered before blood injection and on the 10th day after SAH. TGF-β1, p-Smad2/3, connective tissue growth factor (CTGF), collagen I and pro-collagen I c-terminal propeptide were assessed via western blotting, enzyme-linked immunosorbent assay, radioimmunoassay and immunofluorescence. And neurobehavioral tests and Morris water maze were employed to evaluate long-term neurological functions after SAH. We found that SAH induced heightened activation of TGF-β1/Smad/CTGF axis, presenting as a two peak response of TGF-β1 in cerebrospinal fluid, elevation of TGF-β1, p-Smad2/3, CTGF, collagen I in brain parenchyma and pro-collagen I c-terminal propeptide in cerebrospinal fluid, and increased lateral ventricle index. rhDecorin treatment effectively inhibited up-regulation of TGF-β1, p-Smad2/3, CTGF, collagen I and pro-collagen I c-terminal propeptide after SAH. Moreover, rhDecorin treatment significantly reduced lateral ventricular index and incidence of chronic hydrocephalus after SAH. Importantly, rhDecorin improved neurocognitive deficits after SAH. In conclusion, rhDecorin suppresses extracellular matrix accumulation and following subarachnoid fibrosis via inhibiting TGF-β1/Smad/CTGF pathway, preventing development of hydrocephalus and attenuating long-term neurocognitive defects after SAH.
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lingyong
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jiaode
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guangyong
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: doctorlf@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D058575:Decorin / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D006849:Hydrocephalus / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; C546878:DCN protein, human; D058575:Decorin; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor
keywords: Connective tissue growth factor; Decorin; Hydrocephalus; Subarachnoid fibrosis; Subarachnoid hemorrhage; Transforming growth factor-β1