Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

Jacqueline R. Kulbe, Edward D. Hall

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations


In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, American football, Australian football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression.

Original languageEnglish
Pages (from-to)15-44
Number of pages30
JournalProgress in Neurobiology
StatePublished - Nov 2017

Bibliographical note

Funding Information:
Some of the work cited in this review from the corresponding author’s laboratory was supported by NINDS R01NS046566; P01 NS058484; R01 NS083405 and R01 NS084857. Additionally, the first author is currently supported by NINDS F30 NS096876.

Publisher Copyright:
© 2017 Elsevier Ltd


  • Chronic traumatic encephalopathy
  • Concussion
  • Repetitive head injury
  • Tauopathy
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience (all)


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