Intramantle pressure gradients favoring hydrocephalus development following disruption of integrin-matrix interactions

A problem presented at the Canadian MMSG Toronto 2009.

Presented by:
Dr. Miles Johnston (Sunnybrook Health Sciences Centre)
Participants:
J Arciero, R Begg, K Ferguson, M Johnston, S Naire, B Orser, T Sherk, S Sivaloganathan, K Wilkie, W Yao

Problem Description

Hydrocephalus is a chronic brain disorder characterized by expansion of the ventricles and in some cases, significant neurological damage. Current treatments are only partially effective and there is an urgent need to reassess the conceptual foundation on which our understanding of this disease is based. Perhaps the greatest paradox in the hydrocephalus field is the failure of researchers to consistently measure transmantle pressure gradients in humans and in animal models of the communicating form of the disorder. Without such a gradient it is difficult to conceptualize how ventricular distention occurs.

The overall objective of our work is to investigate the mechanisms responsible for ventricular expansion in a rat model of hydrocephalus. In particular, we have been made aware of the studies performed by Dr. Reed and colleagues in Norway. His experiments demonstrated that the interstitial matrix in skin was an 'active' component in tissue pressure regulation. We surmised that if true in the brain, this matrix concept might provide an explanation for ventriculomegaly.

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Study Group Report

We investigate intramantle pressure gradients as a possible force to enlarge the ventricles and we propose a new poroelastic model incorporating the effect of the antibodies to determine if they are a possible mechanism for hydrocephalus.

Our preliminary investigation seems to indicate that our assumed mechanical alterations resulting from the injection of anti β1 integrin antibodies provides the necessary environmental changes in the parenchyma for the pathogenesis of hydrocephalus. A drop in interparenchymal pressure combined with the required increase in CSF absorption by the parenchyma creates the necessary conditions for ventricular enlargement. Add to this, the possibility that antibodies may decrease the elasticity of brain tissue and even more favourable conditions for hydrocephalus are created.

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