The purpose of the mechanical brain injury and therapy laboratory is to provide an experimental facility for resolving issues which are closely allied with the thrust of the clinical trial. As such, experiments targeted for therapy evaluation are designed to more closely simulate actual conditions at time of injury as well as incorporating delays in treatment which normally occur. In the previous application, we tested the hypothesis that mechanical injury results in the development of tissue acidosis which can adversely effect the external and in-internal milieu necessary for cell functi on we measured, using magnetic resonance spec-troscopy (MRS) and and microsphere CBF, the metabolic response to experimental brain injury and observed that CBF was inadequate to meet oxidative demand resulting in relative ischemia which we attributed to impaired vasoreactivity. Based on this evidence, this application is based on the hypothesis that relative ischemia may be avoided either by improving vessel reactivity or decreasing energy requirements. Two drugs, (PEG-SOD) and THAM proposed for use in the ICU will be evaluated as to their effectiveness in reducing impairment of vessel reactivity and improving CBF to meet demand. We will also provide data to clarify the mechanism by which THAM overcomes the deleterious effect of sustained hyperventilation to allow safe use of this therapy for ICP control. A third drug, Etomidate, will be tested in its ability to lower metabolism and ameliorate relative ischemia by reducing blood flow requirements in the well-defined model of fluid percussion injury. Our goal is to provide data to help determine the effectiveness and the mechanism by which these drugs operate in a well-defined model of experimental brain injury. In this way, we can optimize current deliveryy of therapy and suggest new avenues of treatment for improvement f outcome and morbidity.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
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
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
Hartings, Jed A; Strong, Anthony J; Fabricius, Martin et al. (2009) Spreading depolarizations and late secondary insults after traumatic brain injury. J Neurotrauma 26:1857-66
Mazzeo, Anna Teresa; Brophy, Gretchen M; Gilman, Charlotte B et al. (2009) Safety and tolerability of cyclosporin a in severe traumatic brain injury patients: results from a prospective randomized trial. J Neurotrauma 26:2195-206
Samuelson, Rod; Mazzeo, Anna; Kunene, Nikki et al. (2006) Synthes Award For Resident Research On Craniofacial And Brain Injury: effect of cyclosporin A, topiramate, or 100% oxygen as proposed ""neuroprotective"" therapies on the neurochemical analytes in patients with severe traumatic brain injury. Clin Neurosurg 53:307-12
Stiefel, Michael F; Tomita, Yoshiyuki; Marmarou, Anthony (2005) Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury. J Neurosurg 103:707-14
Stiefel, Michael F; Marmarou, Anthony (2002) Cation dysfunction associated with cerebral ischemia followed by reperfusion: a comparison of microdialysis and ion-selective electrode methods. J Neurosurg 97:97-103
Yamamoto, M; Marmarou, C R; Stiefel, M F et al. (1999) Neuroprotective effect of hypothermia on neuronal injury in diffuse traumatic brain injury coupled with hypoxia and hypotension. J Neurotrauma 16:487-500
Barzo, P; Marmarou, A; Fatouros, P et al. (1997) MRI diffusion-weighted spectroscopy of reversible and irreversible ischemic injury following closed head injury. Acta Neurochir Suppl 70:115-8
Marmarou, A; Barzo, P; Fatouros, P et al. (1997) Traumatic brain swelling in head injured patients: brain edema or vascular engorgement? Acta Neurochir Suppl 70:68-70

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