{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T23:43:05Z","timestamp":1771458185890,"version":"3.50.1"},"reference-count":30,"publisher":"Georg Thieme Verlag KG","issue":"05","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neurol Surg A Cent Eur Neurosurg"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Chronic hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH); however, the risk factors and the mechanisms underlying its occurrence have yet to be fully elucidated. The purpose of this study was to identify biomarkers that could be used to predict chronic hydrocephalus after aSAH and to investigate the relationships.<\/jats:p><jats:p>\n          Methods\u2003We analyzed cerebrospinal fluid (CSF) samples from 19 patients with chronic hydrocephalus after aSAH and 44 controls without hydrocephalus after aSAH. Enzyme-linked immunosorbent assay was used to determine the levels of leucine-rich alpha-2-glycoprotein (LRG), transforming growth factor-\u03b2 (TGF-\u03b2), Smad1, Smad4, Smad5, Smad8, activin receptor-like kinase 1 (Alk-1), activin receptor-like kinase 5 (Alk-5), P38, and TGF-\u03b2 type II receptor (TGF\u00dfRII) in CSF samples.<\/jats:p><jats:p>\n          Results\u2003In the CSF of patients with chronic hydrocephalus after aSAH, the levels of LRG, TGF-\u03b2, Alk-1, Smad5, and TGF\u00dfRII were significantly increased (p\u2009&lt;\u20090.05) and the levels of Smad1, Smad4, and Smad8 were significantly decreased (p\u2009&lt;\u20090.05). There were no significant differences between the two groups concerning the levels of P38 and Alk-5 (p\u2009&gt;\u20090.05). The analysis also identified significant correlations between specific biomarkers: LRG and Smad1, LRG and Smad5, TGF-\u03b2 and Alk-1, and Alk-1 and Smad4 (p\u2009&lt;\u20090.05); the Pearson's correlation coefficients for these relationships were \u22120.341, 0.257, 0.256, and \u22120.424, respectively.<\/jats:p><jats:p>\n          Conclusion\u2003The levels of LRG, TGF-\u03b2, Alk-1, TGF\u00dfRII, Smad1\/5\/8, and Smad4 in the CSF are potentially helpful as predictive biomarkers of chronic hydrocephalus after aSAH. Moreover, the LRG-TGF-\u03b2-Alk-1\/TGF\u00dfRII-Smad1\/5\/8-Smad4 signaling pathway is highly likely to be involved in the pathogenic process of chronic hydrocephalus after aSAH.<\/jats:p>","DOI":"10.1055\/s-0043-1771277","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T22:56:05Z","timestamp":1692658565000},"page":"457-463","source":"Crossref","is-referenced-by-count":3,"title":["The LRG-TGF-\u03b2-Alk-1\/TGF\u00dfRII-Smads as Predictive Biomarkers of Chronic Hydrocephalus after Aneurysmal Subarachnoid Hemorrhage"],"prefix":"10.1055","volume":"85","author":[{"given":"Dongying","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref1","first-page":"8584753","article-title":"Hydrocephalus after subarachnoid hemorrhage: pathophysiology, diagnosis, and treatment","volume":"2017","author":"S Chen","year":"2017","journal-title":"BioMed Res Int"},{"issue":"08","key":"ref2","first-page":"CD001691","article-title":"Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants","volume":"2013","author":"E Smit","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neulet.2006.11.039","article-title":"Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus","volume":"413","author":"X Li","year":"2007","journal-title":"Neurosci Lett"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"a022137","DOI":"10.1101\/cshperspect.a022137","article-title":"Signaling cross talk between TGF-\u03b2\/Smad and other signaling pathways","volume":"9","author":"K Luo","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"12","key":"ref5","first-page":"PR19","article-title":"Comparison of cerebrospinal fluid biomarkers between idiopathic normal pressure hydrocephalus and subarachnoid hemorrhage-induced chronic hydrocephalus: a pilot study","volume":"18","author":"J H Lee","year":"2012","journal-title":"Med Sci Monit"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1080\/14397595.2021.1883841","article-title":"The involvement of leucine-rich \u03b1-2 glycoprotein in the progression of skin and lung fibrosis in bleomycin-induced systemic sclerosis model","volume":"31","author":"H Nakajima","year":"2021","journal-title":"Mod Rheumatol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jss.2020.03.018","article-title":"The prognostic impact of leucine-rich \u03b1-2-glycoprotein-1 in cholangiocarcinoma and its association with the IL-6\/TGF-\u03b21 axis","volume":"252","author":"Z Jin","year":"2020","journal-title":"J Surg Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.brainres.2015.11.004","article-title":"Decorin alleviated chronic hydrocephalus via inhibiting TGF-\u03b21\/Smad\/CTGF pathway after subarachnoid hemorrhage in rats","volume":"1630","author":"H Yan","year":"2016","journal-title":"Brain Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s11010-012-1258-2","article-title":"Neuregulin induces CTGF expression in hypertrophic scarring fibroblasts","volume":"365","author":"J S Kim","year":"2012","journal-title":"Mol Cell Biochem"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jcpa.2013.12.001","article-title":"Comparative study of transforming growth factor-\u03b2 signalling and regulatory molecules in human and canine idiopathic pulmonary fibrosis","volume":"150","author":"L Lilja-Maula","year":"2014","journal-title":"J Comp Pathol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.carpath.2017.07.004","article-title":"Reduced activin receptor-like kinase 1 activity promotes cardiac fibrosis in heart failure","volume":"31","author":"K J Morine","year":"2017","journal-title":"Cardiovasc Pathol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0065-2776(00)75003-6","article-title":"TGF-beta signaling by Smad proteins","volume":"75","author":"K Miyazono","year":"2000","journal-title":"Adv Immunol"},{"issue":"09","key":"ref13","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.tcb.2008.06.006","article-title":"Decoding the quantitative nature of TGF-beta\/Smad signaling","volume":"18","author":"D C Clarke","year":"2008","journal-title":"Trends Cell Biol"},{"issue":"11","key":"ref14","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.1096\/fj.09-131607","article-title":"Casein kinase 2beta as a novel enhancer of activin-like receptor-1 signaling","volume":"23","author":"N Y Lee","year":"2009","journal-title":"FASEB J"},{"issue":"16","key":"ref15","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1101\/gad.12.16.2445","article-title":"Smads and early developmental signaling by the TGFbeta superfamily","volume":"12","author":"M Whitman","year":"1998","journal-title":"Genes Dev"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/s41556-018-0264-3","article-title":"ALK phosphorylates SMAD4 on tyrosine to disable TGF-\u03b2 tumour suppressor functions","volume":"21","author":"Q Zhang","year":"2019","journal-title":"Nat Cell Biol"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1182\/blood-2008-03-143354","article-title":"Iron regulates phosphorylation of Smad1\/5\/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver","volume":"112","author":"L Kautz","year":"2008","journal-title":"Blood"},{"issue":"14","key":"ref18","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.1093\/emboj\/cdf366","article-title":"TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses","volume":"21","author":"L Yu","year":"2002","journal-title":"EMBO J"},{"issue":"07","key":"ref19","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1212\/WNL.0000000000002377","article-title":"Is normal pressure hydrocephalus becoming less idiopathic?","volume":"86","author":"N R Graff-Radford","year":"2016","journal-title":"Neurology"},{"issue":"03","key":"ref20","first-page":"360","article-title":"Evidence for transforming growth factor-beta expression in human leptomeningeal cells and transforming growth factor-beta-like activity in human cerebrospinal fluid","volume":"67","author":"M D Johnson","year":"1992","journal-title":"Lab Invest"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1161\/01.STR.27.5.852","article-title":"Increased expression of TGF-beta 1 in brain tissue after ischemic stroke in humans","volume":"27","author":"J Krupinski","year":"1996","journal-title":"Stroke"},{"issue":"7458","key":"ref22","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature12345","article-title":"LRG1 promotes angiogenesis by modulating endothelial TGF-\u03b2 signalling","volume":"499","author":"X Wang","year":"2013","journal-title":"Nature"},{"issue":"20","key":"ref23","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.21037\/atm-21-4879","article-title":"A narrative review of the relationship between TGF-\u03b2 signaling and gynecological malignant tumor","volume":"9","author":"F Luo","year":"2021","journal-title":"Ann Transl Med"},{"issue":"04","key":"ref24","first-page":"3661","article-title":"High-dose TGF-\u03b21 degrades human nucleus pulposus cells via ALK1-Smad1\/5\/8 activation","volume":"20","author":"Z Qu","year":"2020","journal-title":"Exp Ther Med"},{"issue":"04","key":"ref25","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S1097-2765(03)00386-1","article-title":"Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta\/ALK5 signaling","volume":"12","author":"M J Goumans","year":"2003","journal-title":"Mol Cell"},{"key":"ref26","first-page":"748","article-title":"Up-regulation of miR-155 potentiates CD34+ CML stem\/progenitor cells to escape from the growth-inhibitory effects of TGF-\u00df1 and BMP signaling","volume":"20","author":"T Mahdloo","year":"2021","journal-title":"EXCLI J"},{"key":"ref27","first-page":"81","article-title":"Genetic and molecular pathogenesis of hereditary hemorrhagic telangiectasia","volume":"47","author":"H Azuma","year":"2000","journal-title":"J Med Invest"},{"issue":"05","key":"ref28","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1097\/00006123-199911000-00021","article-title":"Factors associated with hydrocephalus after aneurysmal subarachnoid hemorrhage","volume":"45","author":"J P Sheehan","year":"1999","journal-title":"Neurosurgery"},{"issue":"04","key":"ref29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3340\/jkns.2008.43.4.177","article-title":"Predisposing factors related to shunt-dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage","volume":"43","author":"J H Kwon","year":"2008","journal-title":"J Korean 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