Transforming growth factor-βs in a rat model of neonatal posthaemorrhagic hydrocephalus

Posthaemorrhagic ventricular dilatation (PHVD) is a common complication of intraventricular haemorrhage in premature infants. The aim of this study was to investigate the role of transforming growth factor-betas (TGF-betas), a family of polypeptides with potent desmoplastic properties, in the aetiology of PHVD in a newly developed neonatal rat model of this disorder. Pups were injected with citrated rat blood or artificial cerebrospinal fluid (ACSF) into alternate lateral ventricles on postnatal days 7 and 8. The brains were perfusion-fixed 14 days later and immunohistochemistry was performed for TGF-beta1, -beta2 and -beta3, p44/42 mitogen-activated protein (MAP) kinases, and the extracellular matrix proteins laminin, vitronectin and fibronectin. Ventricular dilatation occurred in 58.3% of animals injected with blood and 36.7% of those injected with ACSF. Periventricular immunoreactivity for TGF-beta1 and -beta2 increased in injected animals irrespective of the presence or absence of ventricular dilatation, although the levels of both isoforms tended to be higher in animals with hydrocephalus. TGF-beta3 immunoreactivity was elevated in hydrocephalic rats only. The immunolabelling for phosphorylated p44/42 MAP kinases rose in a pattern similar to that for TGF-beta1 and -beta2. Expression of TGF-betas was accompanied by deposition of the extracellular matrix proteins fibronectin, laminin and vitronectin. The changes caused by injection of ACSF were the same as those caused by injection of blood. Our results raise the possibility that expression of TGF-betas, together with extracellular matrix protein deposition, may be involved in the development and/or maintenance of hydrocephalus after ventricular distension due to haemorrhage in the neonate.