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Research in the laboratory is directed to understanding cellular mechanisms of brain damage and recovery in acute neurological disorders. Our current work focuses on hypoxic-ischemic injury of the brain's white matter. Relatively little is known about specific pathways leading to structural and functional disruption of axons and glial cells in white matter. We observed that overactivation of glutamate receptors (excitotoxicity) is toxic not only to neurons, but also to oligodendrocytes, the myelin-forming glial cells. We are using cell culture and brain slice models to understand interactions between oligodendrocytes and axons. Conditions as different as stroke, trauma, perinatal brain injury, and multiple sclerosis may share common mechanisms of white matter injury. In addition, we are developing models to study recovery of neurological function after injury by growth of new axons and formation of new synapses in the central nervous system. Experimental methods used in the lab include cell culture, brain slice, and in vivo stroke models. We are developing methods for cell-specific transgenic and viral gene delivery, to visualize cells with advanced optical microscopy techniques such as calcium imaging, digital fluorescence imaging, and multiphoton microscopy. Our lab benefits tremendously from the outstanding collaborative environment provided by the Hope Center for Neurological Disorders and Washington University's neuroscience community.
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