Differential neuropathology and functional outcome after equivalent traumatic brain injury in aged versus young adult mice

Mecca B.A.R. Islam, Booker T. Davis*, Mary J. Kando, Qinwen Mao, Daniele Procissi, Craig Weiss, Steven J. Schwulst

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The CDC estimate that nearly 3 million Americans sustain a traumatic brain injury (TBI) each year. Even when medical comorbidities are accounted for, age is an independent risk factor for poor outcome after TBI. Nonetheless, few studies have examined the pathophysiology of age-linked biologic outcomes in TBI. We hypothesized that aged mice would demonstrate more severe neuropathology and greater functional deficits as compared to young adult mice after equivalent traumatic brain injuries. Young adult (14-week-old) and aged (80-week-old) C57BL/6 male mice underwent an open-head controlled cortical impact to induce TBI or a sham injury. At 30-days post-injury groups underwent behavioral phenotyping, magnetic resonance imaging, and histologic analyses. Contrary to our hypothesis, young adult TBI mice exhibited more severe neuropathology and greater loss of white matter connectivity as compared to aged mice after TBI. These findings correlated to differential functional outcomes in anxiety response, learning, and memory between young adult and aged mice after TBI. Although the mechanisms underlying this age-effect remain unclear, attenuated signs of secondary brain injury in aged TBI mice point towards different inflammatory and repair processes between age groups. These data suggest that age may need to be an a priori consideration in future clinical trial design.

Original languageEnglish (US)
Article number113714
JournalExperimental Neurology
Volume341
DOIs
StatePublished - Jul 2021

Keywords

  • Age
  • Behavior
  • Controlled cortical impact
  • Fear
  • Neurodegeneration
  • Trauma
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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