Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury

Aisling Spain, Stephanie Daumas, Jonathan Lifshitz, Jonathan Rhodes, Peter J.D. Andrews, Karen Horsburgh, Jill H. Fowler

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Mild traumatic brain injury (TBI) accounts for up to 80% of clinical TBI and can result in cognitive impairment and white matter damage that may develop and persist over several years. Clinically relevant models of mild TBI for investigation of neurobiological changes and the development of therapeutic strategies are poorly developed. In this study we investigated the temporal profile of axonal and somal injury that may contribute to cognitive impairments in a mouse model of mild TBI. Neuronal perikaryal damage (hematoxylin and eosin and Fluoro-Jade C), myelin integrity (myelin basic protein and myelin-associated glycoprotein), and axonal damage (amyloid precursor protein), were evaluated by immunohistochemistry at 4 h, 24 h, 72 h, 4 weeks, and 6 weeks after mild lateral fluid percussion brain injury (0.9 atm; righting time 167 ± 15 sec). At 3 weeks post-injury spatial reference learning and memory were tested in the Morris water maze (MWM). Levels of damage to neuronal cell bodies were comparable in the brain-injured and sham groups. Myelin integrity was minimally altered following injury. Clear alterations in axonal damage were observed at various time points after injury. Axonal damage was localized to the cingulum at 4 h post-injury. At 4 and 6 weeks post-injury, axonal damage was evident in the external capsule, and was seen at 6 weeks in the dorsal thalamic nuclei. At 3 weeks post-injury, injured mice showed an impaired ability to learn the water maze task, suggesting injury-induced alterations in search strategy learning. The evolving localization of axonal damage points to ongoing degeneration after injury that is concomitant with a deficit in learning.

Original languageEnglish (US)
Pages (from-to)1429-1438
Number of pages10
JournalJournal of Neurotrauma
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2010

Keywords

  • axonal damage
  • cognition
  • memory
  • mild traumatic brain injury
  • white matter

ASJC Scopus subject areas

  • Clinical Neurology

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