Oxygen-glucose deprivation (OGD) has never before been considered as a potential factor in alcohol related neurological damage. Studies suggest that chronic ethanol exposure prior to OGD-induced toxicity will likely exacerbate OGD-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 OGD-induced toxicity, in particular following prior ethanol exposure. I will first look at these agents against OGD 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 OGD (~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 OGD and alcohol, and also act as a model for the evaluation of potential pharmacological treatments. ? ?
| Stepanyan, Tracy D; Farook, Justin M; Kowalski, Alexandra et al. (2008) Alcohol withdrawal-induced hippocampal neurotoxicity in vitro and seizures in vivo are both reduced by memantine. Alcohol Clin Exp Res 32:2128-35 |
