Mechanism responsible for the formation of focal swellings on injured neuronal processes using a novel in vitro model of axonal injury.

A novel in vitro model of axonal injury using PC12 cells was designed to introduce traumatic alterations on neuronal processes and to identify mechanisms responsible for the formation of focal swellings by observation with phase-contrast and transmission electron microscopes. The injury on the processes was developed by one-dimensional, horizontal oscillation. Phase-contrast microscopic observation on the injured processes showed their terminal increase in diameter. Long term observation of cellular responses to the mechanical insult disclosed that the terminal swelling coincided with the detachment of growth cones from the culture plate. The finding suggests that the detachment of the growth cone would destroy a cytoskeletal network, which determines and maintains the cell shapes, and then cause the spherical deformation of the processes. Ultramicroscopically, the processes with terminal swellings regenerated the growth cones by the cytoskeletal reconstruction.