Biophysical mechanisms that contribute to hydrocephalus development

Hydrocephalus is a chronic brain disorder characterized by the expansion of 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 hydrocephalus. In collaboration with Dr. Pat McAllister's group in the U.S., we are investigating whether there is a relationship between ventriculomegaly and impaired lymphatic function in a kaolin-hydrocephalus model in rats. Concurrent with these studies, we discovered the work conducted by Dr. Reed in Norway, which demonstrates that the interstitial matrix in skin is an “active” component in tissue pressure regulation. We concluded that if true in the brain, this matrix concept might provide an explanation for ventriculomegaly, which then led to studies to determine if trans-parenchymal pressure gradients caused by disruption of brain matrix components represent an important event in causing ventriculomegaly. (These two concepts are linked since lymphatic dysfunction is known to elevate intracranial pressure and this likely exacerbates the trans-parenchymal pressure gradients elicited by some other inciting event.)