Decorin and colchicine as potential treatments for post-haemorrhagic ventricular dilatation in a neonatal rat model.

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 ß (TGFß) in the pathogenesis of PHVD. Colchicine and decorin are both compounds with anti-TGFß properties. The former downregulates TGFß production and is in clinical use for another fibrotic disease, and the latter inactivates TGFß. OBJECTIVES: We hypothesized that administration of decorin or colchicine, which both have anti-TGFß 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 TGFß by different mechanisms do not reduce ventricular dilatation in this model. Together with our previous work on losartan and pirfenidone, we conclude that blocking TGFß alone does not prevent the development of PHVD.