Keywords

 

Authors

  1. Smith, Douglas H. MD
  2. Meaney, David F. PhD
  3. Shull, William H. MD

Abstract

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.

 

DIFFUSE AXONAL INJURY (DAI) is a "stealth" pathology of traumatic brain injury (TBI). Although found throughout the white matter, it comprises primarily microscopic damage, rendering it almost invisible to current imaging techniques. Yet, it is one of the most common and important pathologic features of TBI. It seems ironic that the size and organization of the human brain that allow us to design and drive automobiles are also our greatest liability of producing DAI in the event of a crash. Under the physical forces such as shear that are commonly induce TBI, the human brain can literally pull itself apart. In particular, axons in the white matter appear poorly prepared to withstand damage from rapid mechanical deformation of the brain during trauma. Here, we will explore the current understanding of the causes and pathologic changes associated with DAI. In addition, we will examine deficiencies in our current ability to diagnose, grade, and treat DAI.