Evidence from animal models of alcohol dependence suggests that alcohol-related neurodegeneration occurs primarily during intoxication, not during withdrawal as previously believed (Crews and Nixon, 2009; Obernier et al., 2002). In the oxidative stress model proposed by Crews and Nixon (2009), volume losses in AUDs are attributed to stimulation of proinflammatory cascades leading to cell dysfunction or death and inhibition of neurogenesis in adult neural stem cells located in the olfactory bulb and hippocampus. The observation that alcohol-related brain damage in humans appears to be more closely related to recency of drinking than duration or quantity of drinking lends support to this model (Crews and Nixon, 2009). Evaluating the relative importance of cumulative exposure, measured in duration of AUD or in lifetime consumption, versus recency of exposure is critical to understanding the neurobiology of alcohol-related WM damage and repair.
