The specialized nature of neurons as highly adapted and adaptable cells capable of information processing has ad the result that these cells are extremely vulnerable to rapid changes in their environment. Several of these changes are, hypoxia-ischemia, hypoglycemia, or hyperexcitation, which lead to a cascade of events that may cause neuronal death due to necrosis, and/or apoptosis. Under conditions where glucocorticoid levels are elevated the neurons become sensitized to rapid environmental changes. This proposal is designed to determine if several genes designed and selected to interfere with glucocorticoid endangerment can reduce neurotoxicity enhancement during neuronal injury. To determine if a synergistic reduction in neuronal injury can be achieved by delivering an isoform of the glucose transporter in conjunction with a gene or genes that reduce glucocorticoid endangerment. This combination of genes will also be tested in a cassette that incorporates a glucocorticoid response element, which then acts as a insult inducible promoter activating these genes under conditions of neuroendangerment. This study will determine if this expression can be neuroprotective using a Herpes amplicon system that is capable of long-term expression within neurons.
