Current Understanding and Experimental Approaches to the Study of Repetitive Brain Injury

Abstract

Repetitive traumatic brain injury (TBI) occurs in a considerable number of individuals in the general population, such as athletes involved in contact sports (e.g. boxing, football, hockey and soccer), or child abuse victims. Repeated mild injuries, such as concussions, may cause cumulative damage to the brain and result in long-term cognitive dysfunction. The growing field of repetitive TBI research is reflected in the increased media attention given to reporting incidences of athletes suffering multiple blows to the head, and in several recent experimental studies of repeated mild TBI in vivo. Experimental reports generally demonstrate cellular and cognitive abnormalities after repetitive injury using rodent TBI models. In some cases, data suggests that the effects of a second mild TBI may be synergistic, rather than additive. In addition, some studies have found increases in cellular markers associated with Alzheimer’s disease after repeated mild injuries, which demonstrates a direct experimental link between repetitive TBI and neurodegenerative disease. To complement the findings from humans and in vivo experimentation, my laboratory group has investigated the effects of repeated trauma in cultured brain cells using an in vitro model of stretch-induced mechanical injury. In these studies, cells exhibit cumulative damage when receiving multiple mild injuries. Interestingly, the extent of damage to the cells is dependent on the time between repeated injuries. Although direct comparisons to the clinical situation are difficult to make, these types of repetitive, low-level, mechanical stresses may be similar to insults received by certain athletes, such as boxers, or hockey and soccer players. As this field of TBI research continues to evolve and expand, it is essential that experimental models of repetitive injury replicate injuries in humans as closely as possible. For example, it is important to appropriately model concussive episodes versus even lower-level injuries (such as those that might occur during boxing matches or by heading a ball repeatedly in soccer). Suitable inter-injury intervals are also important parameters to incorporate into studies. Additionally, it is essential to design and utilize proper controls, which can be more of a challenge than experimental approaches to single mild TBI. These issues, as well as an overview of findings from repeated TBI research, are discussed in this chapter.