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Original Paper

Decorin and Colchicine as Potential Treatments for Post-Haemorrhagic Ventricular Dilatation in a Neonatal Rat Model

Hoque N.a · Thoresen M.a, c · Aquilina K.a, b · Hogan S.a · Whitelaw A.a

Author affiliations

aSchool of Clinical Science (Child Health), University of Bristol, St. Michael’s Hospital, and bDepartment of Neurosurgery, Frenchay Hospital, University of Bristol, Bristol, UK; cDepartment of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

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Neonatology 2011;100:271–276

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 10, 2011
Accepted: March 28, 2011
Published online: June 23, 2011
Issue release date: September 2011

Number of Print Pages: 6
Number of Figures: 3
Number of Tables: 0

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

Abstract

Background: Post-haemorrhagic ventricular dilatation (PHVD) after intraventricular haemorrhage (IVH) remains a significant problem in preterm infants. Due to serious disadvantages of ventriculoperitoneal shunt dependence, there is an urgent need for non-surgical interventions. Considerable experimental and clinical evidence implicates transforming growth factor β (TGFβ) in the pathogenesis of PHVD. Colchicine and decorin are both compounds with anti-TGFβ properties. The former downregulates TGFβ production and is in clinical use for another fibrotic disease, and the latter inactivates TGFβ. Objectives: We hypothesized that administration of decorin or colchicine, which both have anti-TGFβ properties, would reduce ventricular dilatation in a model of PHVD. Methods: 142 rat pups underwent intraventricular blood injection on postnatal days (PN) 7 and 8. Sixty-nine pups were randomized to colchicine 20 and 50 µg/kg/day or water by gavage for 13 days. Seventy were randomized to decorin 4 mg/kg or saline by intraventricular injection on PN8 and PN13. At PN21, the ventricular area was measured on coronal brain sections. Negative geotaxis was tested at PN14 in controls and in the decorin study group. Results: Ventricular size was not different between animals receiving either drug or water/saline. Intraventricular blood impaired neuromotor performance, but decorin had no effect. Conclusion: Two drugs that block TGFβ by different mechanisms do not reduce ventricular dilatation in this model. Together with our previous work on losartan and pirfenidone, we conclude that blocking TGFβ alone does not prevent the development of PHVD.

© 2011 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 10, 2011
Accepted: March 28, 2011
Published online: June 23, 2011
Issue release date: September 2011

Number of Print Pages: 6
Number of Figures: 3
Number of Tables: 0

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO


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