The contribution of edema toward brain swelling and intracranial pressure (ICP) rise particularly in cases of traumatic injury and tumor remains a critical problem. In head injured patients, raised ICP is the single most frequent cause of death. Brain edema, by definition is an increase in tissue water which for vasogenic, interstitial, and late ischemic brain edema results in an increase of extracellular fluid. The ultimate goal of this research is to understand the mechanisms by which edema is cleared from injured and diseased brain and the pathways by which this occurs. Knowledge of these mechanisms is fundamental to the development of new approaches to therapy. The complex inter-action of different mechanisms involved in resolution may be isolated by use of the experimental infusion model of brain edema where spatial distribution, total edema volume and chemical composition are precisely controlled. We plan to use this model in combination with gravimetric, chromatographic, electron microscopic, immunocytochemical and magnetic resonance imaging methods; to test hypotheses relating to elucidating mechanisms involved in early and late stages of clearance; to study the role that diffusion and colloid osmotic pressure play in the clearance process; to determine if injury is a necessary trigger for involvement of the astrocyte in clearance of water; and to assess if protein changes free and bound water fraction. This final objective will lead to the refinement of a non-invasive measure of brain edema in humans and will allow us for the first time to quantify edema in the injured brain.

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
Prieto, Ruth; Tavazzi, Barbara; Taya, Keisuke et al. (2011) Brain energy depletion in a rodent model of diffuse traumatic brain injury is not prevented with administration of sodium lactate. Brain Res 1404:39-49
Fazzina, Giovanna; Amorini, Angela M; Marmarou, Christina R et al. (2010) The protein kinase C activator phorbol myristate acetate decreases brain edema by aquaporin 4 downregulation after middle cerebral artery occlusion in the rat. J Neurotrauma 27:453-61
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
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
Marmarou, A; Signoretti, S; Aygok, G et al. (2006) Traumatic brain edema in diffuse and focal injury: cellular or vasogenic? Acta Neurochir Suppl 96:24-9
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

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