title: A MATHEMATICAL ANALYSIS OF PHYSIOLOGICAL AND MOLECULAR MECHANISMS THAT MODULATE PRESSURE GRADIENTS AND FACILITATE VENTRICULAR EXPANSION IN HYDROCEPHALUS.
abstract: Perhaps the greatest paradox in the hydrocephalus field is the failure of researchers to consistently measure transmantle pressure gradients (ventricle to subarachnoid space) in either human or animal models of the communicating form of the disorder. Without such a gradient, conceptualization of how ventricular distention occurs is difficult. Based on evidence from both a mathematical model [35] and experiments in skin [51], we observed that the intraventricular injection of anti-β1integrin antibodies in rat brains results in a reduction of periventricular pressures to values below those monitored in the ventricles. In addition, many of these animals developed hydrocephalus [30]. We conclude that the dissociation of β1integrins from the surrounding matrix fibers generates pressure gradients favouring ventricular expansion suggesting a novel mechanism for hydrocephalus development. Several issues, however, need further clarification. If hydrostatic pressure declines in the periventricular tissues then fluid absorption must occur. Aquaporin-4 (AQP4) is a likely candidate for this absorption as it is the predominant water channel in the brain. Indeed, when capillary function is negated, periventricular interstitial fluid pressures increase after anti-β1integrin antibody administration. This suggests that capillary absorption of parenchymal water may play a pivotal role in the generation of pressure gradients in our hydrocephalus model. Focusing on these issues, we present two poroelastic models to investigate the role of intramantle pressure gradients in ventriculomegaly and to determine if integrin-matrix disassociation represents a complete causative mechanism for hydrocephalus development.
authors: Center of Cancer Systems Biology, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
authors: Kathleen P
authors: KP
authors: Wilkie
authors: Faculty of Medicine, University of Toronto, Department of Laboratory Medicine and Pathobiology, Brain Sciences Program, Sunnybrook Health Sciences Centre, Toronto, ON, CAN.
authors: Gurjit
authors: G
authors: Nagra
authors: Faculty of Medicine, University of Toronto, Department of Laboratory Medicine and Pathobiology, Brain Sciences Program, Sunnybrook Health Sciences Centre, Toronto, ON, CAN.
authors: Miles
authors: M
authors: Johnston
keywords: Aquaporin-4; Brain Biomechanics; Hydrocephalus; Poroelasticity; β1 Integrins