The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy

Anthony Petraglia, Benjamin Plog, Samantha Dayawansa, Matthew Dashnaw, Katarzyna Czerniecka, Corey Walker, Michael Chen, Ollivier Hyrien, Jeffrey Iliff, Rashid Deane, Jason Huang, Maiken Nedergaard

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Background: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. Methods: Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro-and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. Results: Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. Conclusions: The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.

Original languageEnglish (US)
JournalSurgical Neurology International
Issue number1
StatePublished - Jan 1 2014
Externally publishedYes


  • Animal model
  • chronic traumatic encephalopathy
  • concussion
  • pathophysiology
  • repetitive

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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