Reflections on traumatic brain injury research in 2018

Over the past decade, our society has acknowledged that traumatic brain injury (TBI) is a serious health problem. According to the Centers for Disease Control and Prevention, 52,000 people die each year after sustaining such an injury, while 275,000 are hospitalized and 1,365,000 visit an emergency room and are released (www.cdc.gov/). Although many of these injuries are relatively mild and do not lead to continued hospitalization, even “mild” brain injuries result in impaired productivity, changes in cognition, and substantial costs in treatment. TBI is a common outcome of vehicular accidents, single and repeated sports blows to the head, single and repeated whole-body and head impact, combat-related blast, and other injuries. TBI features a broad spectrum of pathologies that share varying degrees of morbidity and mortality. Not surprisingly, the characterization and development of successful therapeutic strategies has been difficult. The Journal of Neuroscience Research devotes this issue to a wide array of studies and reviews that reveal the variety and extent of current research on the effects and treatment of TBI. These include studies on a number of animal species as well as those involving human subjects. The animal studies included in this issue report on species ranging from birds to pigs and include a review of potential large animal models. The variety of animal studies stress that a distinct animal may provide value to understand a specific underlying mechanism. Rodents are most often used to study TBI, and provide important and relevant observations. Nevertheless, other animals are often untapped resources that may extend our understanding of the mechanisms underlying recovery from TBI. For example, Blackshear et al. emphasize the appeal of the zebra finch in studying a brain injury because of their ability to alter steroid hormone production (Blackshear, Giessner, Hayden, & Duncan, 2018). Vink emphasizes large animal models and their significance (Vink, 2018). Larger animals generally have brains of greater size and thicker skulls, which more closely reflect the movement dynamics of human brains. They also generally possess larger amounts of white matter, another important characteristic of human brains. Kajstura et al. provide evidence that serotonergic axons regrow after TBI in rodents (Kajstura, Dougherty, & Linden, 2018). Schwerin et al. show that the ferret presents a strong model to study TBI in a gyrencephalic animal (Schwerin et al., 2018). Perhaps as a reflection of the very heterogeneous nature of TBI causes and outcomes, a broad range of animal models help in understanding the mechanistic and multifaceted nature of TBI to provide platforms for the development and testing of hypotheses conducive to therapeutic interventions. Although the population at risk for TBI is in large measure male, young, and physically fit, there are significant ageand sex-related differences inherent in acute and more chronic outcomes, especially with respect to children, which reflect the impact of TBI on brain development and long-term behavioral outcomes as described by Goodrich-Hunsakera et al. and Yu et al. (Goodrich-Hunsaker et al., 2018; Yu et al., 2018). For example, the study by Van Horn et al. reports a history of pediatric TBI revealing brain morphology similar to early-onset mild cognitive impairment (Van Horn et al., 2018). Yet, even knowing that these inherent differences are present, a critical aspect to the understanding of TBI outcomes is to incorporate an accurate evaluation of patient selfassessment as a measure of trauma status as explored by Vallat-Azouvi et al. (2018). Case studies involving humans can also provide specific information that enhance our understanding of detailed features or specialized treatments. Other studies in this issue clarify the effects of treatments that may, or may not, assist in healing. For example, Crone et al. find that the restoration of thalamocortical connectivity is not specifically related to consciousness, but report that thalamofrontal connectivity may be linked to the return of complex cognitive function (Crone, Bio, Vespa, Lutkenhoff, & Monti, 2018). Joseph et al. review noninvasive treatment strategies and provide an update of their status (Joseph, Khan, & Rhee, 2018). Hamblin provides a review suggesting that photobiomodulation improves memory, mood, and other emotional aspects after TBI (Hamblin, 2018), while Hart et al. find that trials with dextroamphetamine are not encouraging for assisting recovery after TBI (Hart, Whyte, Watanabe, & Chervoneva, 2018). Successful implementation of therapeutic strategies to treat TBI will require an understanding of the various elements that unfold over time after TBI. Given the variety of TBI scenarios, it is clear that there will be a large number of molecular and cellular mechanisms involved with different overlapping roles.