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Our research is focused on two clinical problems in pediatric neurology, perinatal asphyxia, and traumatic brain injury. We use mouse and rat models of perinatal hypoxia-ischemia in the newborn and traumatic brain injury in the young adult mouse to recapitulate these injuries in the laboratory. We use a combination of invasive and non-invasive physiologic monitoring (cerebral blood flow, nitric oxide release, NADH fluorescence; blood pressure) together with molecular and immunohistochemical techniques for these studies.

The overall theme of our work is to enhance the therapy available for the treatment of acute brain injury in children. We have 3 principal areas of interest. First, we have shown that L-carnitine reduces neurologic injury associated with hypoxia-ischemia in the newborn rat. We are now investigating the mechanisms by which hypoxia-ischemia alters mitochondrial carnitine metabolism in the newborn brain. Second, we are studying the contribution of the neuro-inflammatory cascade and glial activation to neurologic injury associated with hypoxia-ischemia and traumatic brain injury. The focus of these studies is the mechanism by which the glial-derived protein, S100B increases glial activation and neurologic injury. Lastly, we are studying the mechanisms regulating the expression of nitric oxide and its contribution to free-radical mediated injury in the developing brain.

Publications:

Wainwright MS, Mannix MK, Brown J and Stumpf DA (2003) L-Carnitine reduces brain injury after hypoxia-ischemia in newborn rats. Pediatr Res 54:688-695

Wainwright MS, Rossi J, Schavocky J, Crawford S, Steinhorn D, Velentza A, Zasadzki M, Shirinsky V, Jia Y, Haiech J, Van Eldik L and Watterson DM (2003) A protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment. Proc Natl Acad Sci 100:6233-6238

Wainwright MS, Brennan L, Dizon M, Black SM (2003) p21ras Activation following hypoxia-ischemia in the newborn rat brain is dependent on nitric oxide synthase activity but p21ras does not contribute to neurologic injury Brain Res Dev Brain Res 146:79-85

Velentza AV, Wainwright MS, Zasadzki M, Mirzoeva S, Haiech J, Focia PJ, Eglia M, Watterson DM (2003) An aminopyridazine based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced brain damage Bioorganic Med Chem Letters 13:3465-3470

Van Eldik L, Wainwright MS (2003) The Janus Face of Glial–derived S100B: Beneficial and Detrimental Functions in the Brain. Restorative Neurology and Neuroscience 21:97-108