Axonal Damage in Traumatic Brain Injury

Abstract

Axonal damage is one of the most common and important pathologic features of traumatic brain injury. Severe diffuse axonal injury, resulting from inertial forces applied to the head, is associated with prolonged unconsciousness and poor outcome. The susceptibility of axons to mechanical injury appears to be due to both their viscoelastic properties and their highly organized structure 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 organelles. Calcium entry into damaged axons is thought to initiate further damage by the activation of proteases and the induction of mitochondrial swelling and dysfunction. Ultimately, swollen axons may become disconnected and contribute to additional neuropathologic changes in brain tissue. However, promising new therapies that reduce proteolytic activity or maintain mitochondrial integrity may attenuate progressive damage of injured axons following experimental brain trauma. Future advancements in the prevention and treatment of traumatic axonal injury will depend on our collective understanding of the relationship between the biomechanics and pathophysiology of various phases of axonal trauma.