Traumatic axonal injury in the optic nerve: evidence for axonal swelling, disconnection, dieback, and reorganization.

Abstract Traumatic axonal injury (TAI) is a major feature of traumatic brain injury (TBI) and is associated with much of its morbidity. To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the nature of TAI within the injured brain precludes the consistent evaluation of its specific anterograde and retrograde sequelae. To overcome this limitation, we used the relatively organized optic nerve in a central fluid percussion injury (cFPI) model. To improve the visualization of TAI, we utilized mice expressing yellow fluorescent protein (YFP) in their visual pathways. Through this approach, we consistently generated TAI in the optic nerve and qualitatively and quantitatively evaluated its progression over a 48-h period in YFP axons via confocal microscopy and electron microscopy. In this model, delayed axonal swelling with subsequent disconnection were the norm, together with the fact that once disconnected, both the proximal and distal axonal segments revealed signifi...