Transforming growth factor-beta 1: A possible signal molecule for posthemorrhagic hydrocephalus?

Posthemorrhagic hydrocephalus remains a complication of preterm birth for w hich we lack a clear understanding and a curative therapy. Transforming gro wth factor beta (TGF-beta) is a cytokine that upregulates the production by fibroblasts of extracellular matrix proteins. We hypothesized that TGF-bet a might be released into cerebrospinal fluid (CSF) after intraventricular h emorrhage and play a role in posthemorrhagic hydrocephalus. Total TGF-beta 1 and TGF-beta 2 were measured by immunoassay in CSF samples from 12 normal preterm infants, nine preterm infants with transient posthemorrhagic ventr icular dilation, and 10 infants who subsequently developed permanent hydroc ephalus. Five infants received intraventricular tissue plasminogen activato r, and two infants were treated by drainage irrigation and fibrinolytic the rapy. Median TGF-beta 1 in normal CSF was 0.495 ng/mL. In infants with tran sient posthemorrhagic ventricular dilation, median initial CSF TGF-beta 1 w as 2.1 ng/mL. Infants who subsequently had permanent hydrocephalus had medi an initial CSF TGF-beta 1, 9.7 ng/mL (differences between groups p < 0.01). Intraventricular recombinant tissue plasminogen activator was followed by a rise in CSF TGF-beta 1 (p = 0.0007). Drainage irrigation and fibrinolytic therapy was followed by a fall in CSF TGF-beta 1. TGF-beta 2 was detected in CSF and showed similar trends, but the CSF concentration of TGF-beta 1 w as more than 20 times higher. These findings support the hypothesis that TG F-beta 1 is released into CSF after intraventricular hemorrhage and may pla y an important pare in hydrocephalus. The results help to explain the failu re of intraventricular fibrinolytic therapy.