Mechanisms of ischemic injury and recovery in white matter axons and glia.

Our research is focused on cellular mechanisms of brain injury and recovery. Many forms of nervous system damage, such as stroke, are mediated by release of the excitatory neurotransmitter, glutamate, and overactivation of glutamate receptors (excitotoxicity). We are examining calcium homeostasis during glutamate receptor activation and the contribution of elevated calcium to subsequent neuronal death. In addition, we use high-resolution fluorescence microscopy to image dendritic structure in living neurons expressing green fluorescent protein. Hypoxia and glutamate receptor stimulation cause rapid dendritic swelling and loss of dendritic spines. Structural changes in dendrites and dendritic spines may contribute to impairment in brain function following stroke. We are now interested in understanding how neurological function may recover by replacement of damaged axons and synapses in the central nervous system.

A current major interest is in hypoxic-ischemic injury of the brain's white matter. We observed that overactivation of glutamate receptors is toxic not only to neurons, but also to oligodendrocytes, the myelin-forming glial cells. We use cell culture and brain slice models to understand toxic interactions between oligodendrocytes and myelinated axons. Conditions as different as stroke, trauma, perinatal brain injury, and multiple sclerosis may share common mechanisms of white matter injury.

Experimental methods used in the lab include cell culture and brain slice models, with special emphasis on advanced optical microscopy techniques such as calcium imaging, digital fluorescence imaging, and multiphoton/confocal microscopy. Our oveall goal is to find new approaches to protect the brain and to enhance recovery after stroke and trauma.