Experimental models of traumatic axonal injury

Traumatic brain injury (TBI) is one of the leading causes of death in people under 45 years of age worldwide. Such injury is characterized by a wide spectrum of mechanisms of injury and pathologies. Traumatic axonal injury (TAI), originally described as diffuse axonal injury, is one of the most common pathological features of TBI and is thought to be responsible for the long-lasting neurological impairments following TBI. Since the late 1980s a series of in vivo and in vitro experimental models of TAI have been developed to better understand the complex mechanisms of axonal injury and to define the relationship between mechanical forces and the structural and functional changes of injured axons. These models are designed to mimic as closely as possible the clinical condition of human TAI and have greatly improved our understanding of different aspects of TAI. The present review summarizes the most widely used experimental models of TAI. Focusing in particular on in vivo models, this survey aims to provide a broad overview of current knowledge and controversies in the development and use of the experimental models of TAI.