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

Abstract

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.

Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP)

“…Another example of tauopathy encephalopathy is associated with CTE. Neurodegeneration with active microglia and inflammatory processes is associated with higher levels of cytokines in the brain tissue and cerebrospinal fluid (CSF) compared with primary tauopathies ( Ling et al, 2015 ; Aldag et al, 2017 ; Makinde et al, 2017 ). This pathology is associated with neurofibrillary tangles.…”

Bibliometric Analysis of Chronic Traumatic Encephalopathy Research from 1999 to 2019

“…In addition, CTE also occurred in military veterans. Statistics showed that more than 300,000 service members and veterans have sustained at least one blast-and/or impact-related traumatic brain injury because of the widespread use of conventional and improvised explosive devices (IED) in the conflicts in Iraq and Afghanistan [33]. Goldstein's study suggested that blast exposure may increase risk for later development of CTE and associated neurobehavioral sequelae [14].…”

Chronic Traumatic Encephalopathy in Professional American Football Players: Where Are We Now?

“…American Football involves repetitive head trauma causing the brain to experience acceleration and deceleration forces ( 14 , 17 , 18 ), leading to coup/countercoup injuries. This can manifest in varying severity from concussions, or concussions of lesser magnitude (sub-concussion) to loss of consciousness ( 19 ).…”

“…However, although documented cases of CTE are characterized by repetitive brain trauma, not all athletes exposed to brain trauma will necessarily develop CTE ( 39 ). Additionally, the frequency, duration, and magnitude of brain injury necessary to elicit the manifestations of CTE are not well understood in the literature ( 17 , 19 ).…”