Progression to Cell Death Correlates with Neurite Swelling Induced by Stretch Injury

Abstract

Diffuse axonal injury (DAI), a major component of traumatic brain injury, is associated with rapid deformation of brain tissue resulting in the stretching of neural axons. Focal axonal swelling, which is the morphological hallmarks of DAI pathology, leads to the disconnection of neurons from tissues, resulting in cell death. Our goal is better understanding of neuronal tolerance and help to predicting the pathogenesis of DAI from mechanical loading to the head. In present study, we developed an in vitro stretch injury device that subjected cultured cells to a wide range of mechanical stretch that are experienced during in vivo head injury. Then using this device, PC12 cells, which extend structurally axon-like cylindrical protrusions in culture, were stretched to a strain of 0.15, 0.30, or 1.00 at strain rates of 30, 40, or 80 s-1, or left as static culture. Following mechanical loading, we assessed neurite swelling resulting in neuronal detachment from culture substrate and neuronal death. As a result, the increase in early neurite swelling was dependent on the severity of the stretch, and neuronal adhesion and viability at 24 h post-injury decrease in a stretch-dependent manner. These results suggest that the formation of neurite swellings correlates with the progression to neuronal death.

Keywords

• diffuse axonal injury
• stretch injury
• neurite swelling
• cell viability
• cell death
• strain
• strain rate
• pc12 cells