Diffuse Axonal Injury in Head Trauma

Background: Diffuse axonal injury (DAI) is one of the most common and important pathologic features of traumatic brain injury (TBI). The susceptibility of axons to mechanical injury appears to be due to both their viscoelastic properties and their high organization in white matter tracts. Although axons are supple under normal conditions, they become brittle when exposed to rapid deformations associated with brain trauma. Accordingly, rapid stretch of axons can damage the axonal cytoskeleton resulting in a loss of elasticity and impairment of axoplasmic transport. Subsequent swelling of the axon occurs in discrete bulb formations or in elongated varicosities that accumulate transported proteins. Calcium entry into damaged axons is thought to initiate further damage by the activation of proteases. Ultimately, swollen axons may become disconnected and contribute to additional neuropathologic changes in brain tissue. DAI may largely account for the clinical manifestations of brain trauma. However, DAI is extremely difficult to detect noninvasively and is poorly defined as clinical syndrome. Conclusions: Future advancements in the diagnosis and treatment of DAI will be dependent on our collective understanding of injury biomechanics, temporal axonal pathophysiology, and its role in patient outcome.