Volume 3, Issue 1
A Mathematical Analysis of Physiological and Molecular Mechanisms that Modulate Pressure Gradients a

KATHLEEN P. WILKIE, GURJIT NAGRA, AND MILES JOHNSTON

Int. J. Numer. Anal. Mod. B, 3 (2012), pp. 65-81

Published online: 2012-03

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  • 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 diffcult. Based on evidence from both a mathematical model [35] and experiments in skin [51], we observed that the intraventricular injection of anti-β_1 integrin 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 β_1 integrins 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 uid 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 uid pressures increase after anti-β_1 integrin 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.
  • AMS Subject Headings

74F10 74F25 92C10 92C45

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@Article{IJNAMB-3-65, author = {KATHLEEN P. WILKIE, GURJIT NAGRA, AND MILES JOHNSTON}, title = {A Mathematical Analysis of Physiological and Molecular Mechanisms that Modulate Pressure Gradients a}, journal = {International Journal of Numerical Analysis Modeling Series B}, year = {2012}, volume = {3}, number = {1}, pages = {65--81}, 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 diffcult. Based on evidence from both a mathematical model [35] and experiments in skin [51], we observed that the intraventricular injection of anti-β_1 integrin 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 β_1 integrins 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 uid 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 uid pressures increase after anti-β_1 integrin 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.}, issn = {}, doi = {https://doi.org/}, url = {http://global-sci.org/intro/article_detail/ijnamb/271.html} }
TY - JOUR T1 - A Mathematical Analysis of Physiological and Molecular Mechanisms that Modulate Pressure Gradients a AU - KATHLEEN P. WILKIE, GURJIT NAGRA, AND MILES JOHNSTON JO - International Journal of Numerical Analysis Modeling Series B VL - 1 SP - 65 EP - 81 PY - 2012 DA - 2012/03 SN - 3 DO - http://doi.org/ UR - https://global-sci.org/intro/article_detail/ijnamb/271.html KW - Hydrocephalus KW - β_1 Integrins KW - Aquaporin-4 KW - Brain Biomechanics KW - Poroelasticity AB - 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 diffcult. Based on evidence from both a mathematical model [35] and experiments in skin [51], we observed that the intraventricular injection of anti-β_1 integrin 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 β_1 integrins 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 uid 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 uid pressures increase after anti-β_1 integrin 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.
KATHLEEN P. WILKIE, GURJIT NAGRA, AND MILES JOHNSTON. (2012). A Mathematical Analysis of Physiological and Molecular Mechanisms that Modulate Pressure Gradients a. International Journal of Numerical Analysis Modeling Series B. 3 (1). 65-81. doi:
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