Neuronal injury resulting from mechanical deformation is poorly characterized at the cellular level. The immediate structural consequences of the mechanical loading lead to a variety of inter- and intra-cellular signaling events that interact on multiple time and length scales. Thus, it is often difficult to establish cause-and-effect relationships such that appropriate treatment strategies can be devised. In this report, we showed that treating mechanically injured neuronal cells with an agent that promotes the resealing of disrupted plasma membranes rescues them from death at 24 h post-injury. A new in vitro model was developed to allow uniform mechanical loading conditions with precisely controlled magnitude and onset rate of loading. Injury severity increased monotonically with increasing peak shear stress and was strongly dependent on the rate of loading as assessed with the MTT cell viability assay, 24 h post-injury. Mechanical injury produced an immediate disruption of membrane integrity as indicated by a rapid and transient release of LDH. For the most severe injury, cell viability decreased approximately 40% with mechanical trauma compared to sham controls. Treatment of cells with Poloxamer 188 at 15 min post-injury restored long-term viability to control values. These data establish membrane integrity as a novel therapeutic target in the treatment of neuronal injury.