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. Author manuscript; available in PMC: 2010 Oct 15.
Published in final edited form as: Biol Psychiatry. 2009 Jul 3;66(8):785–794. doi: 10.1016/j.biopsych.2009.05.021

Figure 8. A proposed model of EW-induced neurodegeneration.

Figure 8

In basal conditions tPA is stored intracellularly, and is released into the extracellular space following EtOH administration (see Fig 1). During intoxication, EtOH (gray circles) blocks NMDA receptors (black circles) and together with extracellular tPA (see (11) is responsible for their upregulation. Abrupt withdrawal of EtOH leaves NMDA receptors unblocked, and the resulting hyperexcitability causes further release of tPA from neurons (see Fig 1). High extracellular levels of tPA activate plasminogen to plasmin, which in turn degrades a component of extracellular matrix, laminin (see Fig 6). Laminin γ-1 degradation renders neurons more sensitive to damaging effects of EW, which results in caspase-3-dependent cell death, while the absence of laminin γ-1 is protective (see Fig 7).