Fellowship Tracy Stepanyan: "Alcohol and a Model of Ischemic Brain Damage"

Oxygen-glucose deprivation (OGO) has never before been considered as a potential factor in alcohol related neurological damage. Studies suggest that chronic ethanol exposure prior to OGO-induced toxicity will likely exacerbate OGO-induced neurotoxicity via pathological excitation of NMDARs. The objective of this proposal is to examine agents, which inhibit the effects of polyamines on NMDARs. These agents will likely be neuroprotective in vitro and in vivo against OGO-induced toxicity, in particular following prior ethanol exposure. I will first look at these agents against OGO alone within the hippocampal slice culture model. Next, cultures will be exposed chronically to ethanol and then, following removal of ethanol, the cultures will be exposed to OGO (-1.5hr). Toxicity will be assessed using the non-vital fluorescent dye propidium iodide. These in vitro studies will be followed by in vivo studies that will evaluate if the agents that were effective in vitro reduce the behavioral deficits associated with alcohol exposure in vivo. The studies proposed both investigate the mechanism for potential interactions between OGO and alcohol, and also act as a model for the evaluation of potential pharmacological treatments.