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.

Keywords:
Colchicine, Decorin, Hydrocephalus, Intraventricular haemorrhage, Newborn, Post-haemorrhagic ventricular dilatation, Transforming growth factor β
This content is only available via PDF.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.