Regional neurodegeneration and gliosis are amplified by mild traumatic brain injury repeated at 24-hour intervals

Amanda N. Bolton, Kathryn E. Saatman

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Most traumatic brain injuries (TBIs) that occur every year are classified as ''mild.'' Individuals involved in high-risk activities may sustain multiple mild TBIs. We evaluated the acute physiologic and histopathologic consequences of mild TBI in a mouse model, comparing sham injury, single impact, or 5 impacts at a 24- or 48-hour interinjury interval. A single closed skull impact resulted in bilateral gliosis in the hippocampus and entorhinal cortex that was proportional to impact depth. Midline impact, at a depth just above the threshold to induce transient unconsciousness, produced occasional axonal injury and degenerating neurons accompanied by astrogliosis in the entorhinal cortex and cerebellum. Mild TBI repeated every 24 hours resulted in bilateral hemorrhagic lesions in the entorhinal cortex along with significantly increased neurodegeneration and microglial activation despite diminished durations of apnea and unconsciousness with subsequent impacts. Astrogliosis and diffusely distributed axonal injury were also observed bilaterally in the cerebellum and the brainstem. When the interval between mild TBIs was increased to 48 hours, the pathologic consequences were comparable to those of a single TBI. Together, these data suggest that, in mice, the brain remains at an increased risk for damage for 24 hours after mild TBI despite reduced acute physiologic responses to subsequent mild impacts.

Original languageEnglish
Pages (from-to)933-947
Number of pages15
JournalJournal of Neuropathology and Experimental Neurology
Issue number10
StatePublished - 2014

Bibliographical note

Publisher Copyright:
Copyright © 2014 by the American Association of Neuropathologists, Inc.


  • Astrocytosis
  • Axonal injury
  • Cerebellum
  • Concussion
  • Entorhinal cortex
  • Loss of consciousness
  • Microgliosis
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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