Brain edema, by definition, is an increase in tissue water which for vasogenic, interstitial or late ischemic brain edema results in an increase of extracellular fluid volume. The objective of the proposed research is to learn how the tissue responds mechanically to the excess water and to what extend biomechanical factors influence the formation, spread, and resolution of edema. These factors are complex and interactive; however, it is possible to isolate these mechanisms by use of infusion edema model where spatial distribution, total edema value, rate of edema formation and chemical composition of the edema can be controlled. We plan to study the dynamics of edema resolution by introducing fluids of known volume and protein content into the brain and describe the time course of fluid clearance in early and late stages of resolution process. Additional viscoelastic studies describing mechanical alterations of brain tissue passively involved in bulk flow will be conducted to identify areas of brain selectively vulnerable to distortion under normal pressure conditions. The pressure effects of the edema and the attendant changes in tissue properties will be characterized to test the proposed therapeutic maneuver of lowering intracranial pressure to enhance fluid clearance. Knowledge of brain edema dynamics should suggest new approaches to therapy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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Virginia Commonwealth University
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Marmarou, Christina R; Liang, Xiuyin; Abidi, Naqeeb H et al. (2014) Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury. Brain Res 1581:89-102
Filippidis, Aristotelis S; Liang, Xiuyin; Wang, Weili et al. (2014) Real-time monitoring of changes in brain extracellular sodium and potassium concentrations and intracranial pressure after selective vasopressin-1a receptor inhibition following focal traumatic brain injury in rats. J Neurotrauma 31:1258-67
Kleindienst, Andrea; Dunbar, Jana G; Glisson, Renee et al. (2013) The role of vasopressin V1A receptors in cytotoxic brain edema formation following brain injury. Acta Neurochir (Wien) 155:151-64
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Taya, Keisuke; Marmarou, Christina R; Okuno, Kenji et al. (2010) Effect of secondary insults upon aquaporin-4 water channels following experimental cortical contusion in rats. J Neurotrauma 27:229-39
Marmarou, Anthony; Signoretti, Stefano; Fatouros, Panos P et al. (2006) Predominance of cellular edema in traumatic brain swelling in patients with severe head injuries. J Neurosurg 104:720-30
Kleindienst, A; Fazzina, G; Dunbar, J G et al. (2006) Protective effect of the V1a receptor antagonist SR49059 on brain edema formation following middle cerebral artery occlusion in the rat. Acta Neurochir Suppl 96:303-6
Kleindienst, A; Dunbar, J G; Glisson, R et al. (2006) Effect of dimethyl sulfoxide on blood-brain barrier integrity following middle cerebral artery occlusion in the rat. Acta Neurochir Suppl 96:258-62
Kleindienst, A; Fazzina, G; Amorini, A M et al. (2006) Modulation of AQP4 expression by the protein kinase C activator, phorbol myristate acetate, decreases ischemia-induced brain edema. Acta Neurochir Suppl 96:393-7

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