Traumatic injury to neurons, initiated by high strain rates, consists of both primary and secondary damage, yet the cellular tolerances in the acute post-injury period are not well understood. The events that occur at the time of and immediately after an insult depend on the injury severity as well as inherent properties of the cell and tissue. We have analyzed neuronal plasma membrane disruption in several in vitro and in vivo injury models of traumatic injury. We found that insult severity positively correlated with the degree of membrane disruptions and that the time course of membrane breaches and subsequent repair varies. This approach provides an experimental framework to investigate injury tolerance criteria as well as mechanistically driven therapeutic strategies. It is postulated that a traumatic insult to the brain or spinal cord results in cellular membrane strain, inducing acute damage that upsets plasma membrane homeostasis. An increased understanding of the pathophysiological mechanisms involved in membrane damage is required in order to specifically target these pathways for diagnostic and treatment purposes and overcome current clinical limitations in the treatment of traumatic brain injury (TBI) and traumatic spinal cord injury (SCI).