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 down- regulates 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, that 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 were randomised to colchicine 20µg/kg/day, 50μg/kg/day or water by gavage for 13 days. Seventy were randomized to decorin 4mg/kg or saline by intraventricular injection on PN8 and PN13. At PN21, ventricular area was measured on coronal brain sections. Negative geotaxis was tested at PN14 in controls and in the decorin study. 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 blocking TGFβ alone does not prevent the development of PHVD.
|Translated title of the contribution||Decorin and Colchicine as potential treatments for post-haemorrhagic ventricular dilatation: Evaluation in a neonatal rat model|
|Pages (from-to)||271 - 276|
|Number of pages||6|
|Publication status||Published - Jun 2011|