A new conceptual foundation for ventricular expansion in the development of hydrocephalus

Koh, Lena; Min Hui Kim; Nagra, Gurjit; Johnston, Miles
July 2007
Journal of Pediatric Neurosciences;Jul-Dec2007, Vol. 2 Issue 2, p101
Academic Journal
Hydrocephalus is a family of disorders characterized by an expansion of the ventricles within the brain. Most investigators have thought cerebrospinal fluid (CSF) malabsorption as the most likely cause of hydrocephalus. However, because the ventricular and subarachnoid compartments are connected, an obstruction in the outflow of CSF would cause an equal increase in pressure, rather than creating a pressure pressure gradient between the two compartments. Indeed, researchers have consistently failed to measure transmantle pressure gradients favouring ventricular expansion in humans and in animal models of hydrocephalus. Alternatively, one group has proposed that ventricular expansion may result from the formation of an intra-mantle, rather than a transmantle, pressure gradient caused by a relative reduction in interstitial pressure in the peri-ventricular area. At present, this concept has received little attention but evidence derived from studies in other tissues may provide a mechanism to explain how ventricular-parenchymal pressure gradients could be formed. β1 integrins, a component of the integrin complex and a major player in interstitial pressure regulation, are found throughout the brain and are believed to have an important role in brain development. We hypothesized that a perturbation of the β1 integrin-matrix interaction may result in a drop in parenchymal interstitial pressure in the peri-ventricular area leading to a pressure gradient favouring the expansion of the ventricles and the movement of CSF from the ventricles into the peri-ventricular tissues (edema). To test this, we injected anti-β1 integrin antibodies, anti-α2βl integrin antibodies and cytochalasin D toxin (n = 12, 4, 8) into the ventricular system of adult Wistar rats. After two weeks, the animals were sacrificed, the brains removed and measured for hydrocephalus. We observed. hydrocephalus development in 13 animals. These results suggest that our novel hypothesis may have some merit and further experiments are designed to test this concept in more detail.


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