Modelling and preventing the development of chronic communicating hydrocephalus

Botfield, Hannah Florence (2014). Modelling and preventing the development of chronic communicating hydrocephalus. University of Birmingham. Ph.D.

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Abstract

In post-haemorrhagic communicating hydrocephalus, CSF drainage is obstructed by subarachnoid fibrosis in which the fibrogenic cytokine transforming growth factor-β1 (TGF-β1) has been aetiologically implicated. Here, the hypothesis that the TGF-β antagonist Decorin has therapeutic potential for (1) reducing fibrosis and the development of hydrocephalus and (2) degrading fibrosis and resolving hydrocephalus, was tested using a rat model of juvenile communicating hydrocephalus.

In the acute study, hydrocephalus was induced by a basal cistern injection of kaolin in 3-week-old rats, immediately followed by continuous intraventricular infusion of either human recombinant Decorin or PBS. In the chronic study, hydrocephalus was allowed to develop for 7 days before starting the treatment of Decorin or PBS. Ventricular expansion was measured by magnetic resonance imaging. Inflammation, fibrosis, Decorin, TGF-β/Smad2/3 activation and hydrocephalic brain pathology were evaluated by immunohistochemistry and basic histology.
In the acute study continuous Decorin infusion prevented the development of hydrocephalus by blocking TGF-β- induced subarachnoid fibrosis and protected against hydrocephalic brain damage. In the chronic study Decorin had no impact on hydrocephalus, TGF-β1 levels or subarachnoid fibrosis, however the efficiency of Decorin infusion was in disrepute.
The results suggest that Decorin is a potential clinical therapeutic for the prevention of juvenile post-haemorrhagic communicating hydrocephalus.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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