Diffuse axonal injury, an important predictor of outcome (Graham et al., 2002), evolves over hours to days and is characterized by axonal swellings and bulbs (Hurley et al., 2004). Primary axotomy, that is, the severing of an axon, is rare in human TBI and is associated with severe TBI. Diffuse axonal injury may culminate in axotomy, but this process is likely delayed in onset, beginning 12–24 hours after injury (Moppett, 2007). It was originally thought that mechanically induced damage to axons impaired axonal transport and that this impairment led to axonal swelling and ultimately axonal disconnection. Recent work, however, has shed light on the pathobiology of axonal injury (Povlishock and Katz, 2005). Although tearing of the axon may occur, it is usually limited to more severe injuries. Rather, axonal injury evolves as a consequence of focal changes in the plasmalemma, including altered permeability, which ultimately impede axonal transport. Data suggest that altered axolemmal permeability allows the influx in calcium and the subsequent activation of proteases that then disrupt the cytoskeleton. Under conditions of normal transport kinetics, focal swelling occurs as a consequence of the buildup of transported molecules and leads ultimately to disconnection of the axon.
Traumatic axonal swellings are not the only indicator of axonal damage. In fact, cytoskeletal perturbations after TBI need not culminate in axonal swellings (Povlishock and Katz, 2005). Rather, there may be a switch from anterograde to retrograde transport, which prevents the buildup of transported molecules (Povlishock and Katz, 2005). The complexity of axonal injury is also evidenced by recent studies of unmyelinated fiber tracts that showed that ionic dysregulation contributes to impairment of anterograde transport (Iwata et al., 2004). There are also data that show that unmyelinated, small-caliber axons may be particularly vulnerable to TBI (Reeves et al., 2005) and may play an important role in morbidity.
Hypoxia, brain swelling, and vascular injury are also seen in diffuse injuries (see above as a description of those events is provided in more detail).
Human head injury is also categorized according to the type of primary injury, either closed (blunt and not caused by a missile) or penetrating injuries (Graham et al., 2002; Morales et al., 2005) (Figure 2.2).
Closed injury includes static and dynamic loading. Static loading occurs when a gradual force is applied to the brain whereas dynamic loading is characterized by rapid acceleration and deceleration. Static loading is not common in human head injury. It may occur in victims of natural disasters, such as earthquakes and landslides, who become trapped under heavy debris. In such a scenario, the head is particularly vulnerable to injury imposed by a gradual force, greater than 200 ms (Graham et al., 2002).
Dynamic loading is more common in human brain injury and is associated with rapid acceleration and deceleration of the brain (Graham et al., 2002). In contrast with static loading, the forces associated with dynamic loading occur in less than 200 ms. Outcome is governed by tissue strain, which is defined as the amount of deformation that occurs as a consequence of the force applied to the brain (Graham et al., 2002; Morales et al., 2005).