Axonal injury is a common feature of mild, moderate, and severe head injury.1 Damage of the axonal pathways within the brain accounts for much of the morbidity after head injury with outcomes ranging from mild concussion to profound coma and even vegetative state. Despite this, the pathogenesis of traumatically induced axonal injury remains unclear.

For many years it was assumed that the rapid acceleration and deceleration of the brain during traumatic injury sheared axons at the time of injury causing them to retract and expel a ball of axoplasm, forming a reactive axonal swelling or retraction ball, the traditional histological feature of diffuse axonal injury.2-6However, more contemporary investigations have not supported the basic concept of axonal shearing at the time of injury as the mode of disconnection.7-12 Rather, they have shown that in most cases of traumatically induced axonal injury, the process of axonal disconnection is not immediate but delayed for four to 24 hours depending on the severity of injury and the species examined.1 This process is known as delayed or secondary axotomy. The traumatic insult elicits a focal axonal abnormality that leads to the impairment of axoplasmic transport with subsequent swelling of the axon.7 This progresses to separation of the swollen axon into a proximal segment in continuity with the sustaining soma and a distal appendage which will undergo Wallerian degeneration. When, in the above described sequence of axonal change, axonal detachment does occur, the continued delivery of axoplasmic constituents via anterograde transport allows for the continued expansion of the proximal swollen axonal segment, which matures into a retraction ball of classic description.7 8

Despite general agreement regarding the occurrence of secondary axotomy there has been little consensus with regard to the pathogenesis of the initiating subcellular events involved in this …