Popis: |
In the United States over 1.7 million cases of traumatic brain injury are reported yearly, but predictive correlation of cellular injury to impact tissue strain is still lacking, particularly for diffuse axonal injury. This information is critically important for the development of mitigation and diagnosis strategies. Using a 3D in vitro neuronal compression model, we investigated the role of impact strain and strain rate on neuronal lifetime, viability, and pathomorphology. We find that strain magnitude and strain rate have profound, yet distinctively different effects on the injury pathology. While strain magnitude determines the time of neuronal death, strain rate governs the pathomorphology and extent of population injury. Cellular injury is not initiated through localized deformation of the cytoskeleton but rather driven by excess strain on the entire cell. Similarly important, mechanoporation, one of the key pathological trigger mechanisms in stretch and shear neuronal injuries, does not occur under compression. |