Preclinical modelling of militarily relevant traumatic brain injuries: Challenges and recommendations for future directions.

As a follow-up to the 2008 state-of-the-art (SOTA) conference on traumatic brain injuries (TBIs), the 2015 event organized by the United States Department of Veterans Affairs (VA) Office of Research and Development (ORD) analysed the knowledge gained over the last 7 years as it relates to basic scientific methods, experimental findings, diagnosis, therapy, and rehabilitation of TBIs and blast-induced neurotraumas (BINTs). The current article summarizes the discussions and recommendations of the scientific panel attending the Preclinical Modeling and Therapeutic Development Workshop of the conference, with special emphasis on factors slowing research progress and recommendations for ways of addressing the most significant pitfalls.

The Biological Basis of Chronic Traumatic Encephalopathy following Blast Injury: A Literature Review.

The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury. It served to inform participants objectively and help focus meeting discussion on identifying knowledge gaps and priority research areas. CTE is described generally as a progressive neurodegenerative disorder affecting persons exposed to head injury. Affected individuals have been participants primarily in contact sports and military personnel, some of whom were exposed to blast. The symptomatology of CTE overlaps with Alzheimer's disease and includes neurological and cognitive deficits, psychiatric and behavioral problems, and dementia. There are no validated diagnostic criteria, and neuropathological evidence of CTE has come exclusively from autopsy examination of subjects with histories of exposure to head injury. The perivascular accumulation of hyperphosphorylated tau (p-tau) at the depths of cortical sulci is thought to be unique to CTE and has been proposed as a diagnostic requirement, although the contribution of p-tau and other reported pathologies to the development of clinical symptoms of CTE are unknown. The literature on CTE is limited and is focused predominantly on head injuries unrelated to blast exposure (e.g., football players and boxers). In addition, comparative analyses of clinical case reports has been challenging because of small case numbers, selection biases, methodological differences, and lack of matched controls, particularly for blast-exposed individuals. Consequently, the existing literature is not sufficient to determine whether the development of CTE is associated with head injury frequency (e.g., single vs. multiple exposures) or head injury type (e.g., impact, nonimpact, blast-related). Moreover, the incidence and prevalence of CTE in at-risk populations is unknown. Future research priorities should include identifying additional risk factors, pursuing population-based longitudinal studies, and developing the ability to detect and diagnose CTE in living persons using validated criteria.