title: 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 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Clinical Science (Child Health), University of Bristol, St. Michael's Hospital, Bristol, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hoque
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
authors.forename: Kristian
authors.initials: K
authors.lastname: Aquilina
authors.forename: Sarah
authors.initials: S
authors.lastname: Hogan
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitelaw
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000473:pathology; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000473:pathology; D003078:Colchicine / Q000008:administration & dosage / Q000494:pharmacology*; D058575:Decorin / Q000008:administration & dosage / Q000494:pharmacology*; D004108:Dilatation, Pathologic / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D018466:Gravity Sensing / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008136:Longevity / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D057897:Reflex, Righting / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D058575:Decorin; D016212:Transforming Growth Factor beta; D003078:Colchicine