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Here, the hypothesis that the transforming growth factor-\u03b2 antagonist decorin has therapeutic potential for reducing fibrosis and ventriculomegaly was tested using a rat model of juvenile communicating hydrocephalus. Hydrocephalus was induced by a single basal cistern injection of kaolin in 3-week-old rats, immediately followed by 3 or 14 days of continuous intraventricular infusion of either human recombinant decorin or phosphate-buffered saline (vehicle). Ventricular expansion was measured by magnetic resonance imaging at Day 14. Fibrosis, transforming growth factor-\u03b2\/Smad2\/3 activation and hydrocephalic brain pathology were evaluated at Day 14 and the inflammatory response at Days 3 and 14 by immunohistochemistry and basic histology. Analysis of ventricular size demonstrated the development of hydrocephalus in kaolin-injected rats but also revealed that continuous decorin infusion prevented ventricular enlargement, such that ventricle size remained similar to that in intact control rats. Decorin prevented the increase in transforming growth factor-\u03b21 and phosphorylated Smad2\/3 levels throughout the ventricular system after kaolin injection and also inhibited the deposition of the extracellular matrix molecules, laminin and fibronectin in the subarachnoid space. In addition, decorin protected against hydrocephalic brain damage inferred from attenuation of glial and inflammatory reactions. Thus, we conclude that decorin prevented the development of hydrocephalus in juvenile rats by blocking transforming growth factor-\u03b2-induced subarachnoid fibrosis and protected against hydrocephalic brain damage. The results suggest that decorin is a potential clinical therapeutic for the treatment of juvenile post-haemorrhagic communicating hydrocephalus.<\/jats:p>","DOI":"10.1093\/brain\/awt203","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T09:19:38Z","timestamp":1377595178000},"page":"2842-2858","source":"Crossref","is-referenced-by-count":92,"title":["Decorin prevents the development of juvenile communicating hydrocephalus"],"prefix":"10.1093","volume":"136","author":[{"given":"Hannah","family":"Botfield","sequence":"first","affiliation":[{"name":"1 1 Neurotrauma and Neurodegeneration, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"1 1 Neurotrauma and Neurodegeneration, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Abdullah","sequence":"additional","affiliation":[{"name":"2 2 Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders D\u00e6hli","family":"Skjolding","sequence":"additional","affiliation":[{"name":"3 3 University Clinic of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Berry","sequence":"additional","affiliation":[{"name":"1 1 Neurotrauma and Neurodegeneration, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"James Pat","family":"McAllister","sequence":"additional","affiliation":[{"name":"2 2 Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"4 4 Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Utah, Salt Lake City, UT 84132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Logan","sequence":"additional","affiliation":[{"name":"1 1 Neurotrauma and Neurodegeneration, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,26]]},"reference":[{"key":"2026071504405071100_awt203-B1","first-page":"36","article-title":"Image Processing with ImageJ","volume":"11","author":"Abramoff","year":"2004","journal-title":"Biophotonics Int"},{"key":"2026071504405071100_awt203-B2","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/j.1651-2227.2008.00903.x","article-title":"Do drugs that block transforming growth factor beta reduce posthaemorrhagic ventricular dilatation in a neonatal rat model?","volume":"97","author":"Aquilina","year":"2008","journal-title":"Acta Paediatr"},{"key":"2026071504405071100_awt203-B3","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1016\/S0021-9258(18)32345-7","article-title":"Transforming growth factor-beta in human platelets. 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