Differential behavioral and histopathological responses to graded cortical impact injury in mice

Kathryn E. Saatman, Kristofer J. Feeko, Rebecca L. Pape, Ramesh Raghupathi

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Controlled cortical impact (CCI) injury, a model of contusive brain injury in humans, is being used with increasing frequency in mice to investigate post-traumatic cell damage and death and to evaluate treatment strategies. Because cellular injury mechanisms and therapeutic approaches may depend on the severity of the initial insult, it is important to utilize a model in which outcomes are sensitive to injury severity. Adult male C57BI/6 mice were anesthetized and subjected to sham injury (n = 23) or CCI injury at either 0.5 mm (n = 22) or 1.0 mm (n = 22) depth of impact at a velocity of 5 m/sec. At 2 days, brain-injured mice exhibited significant memory (p < 0.05) and motor function (p < 0.001) deficits compared to sham-injured mice; furthermore, mice subjected to an impact of 1.0 mm were significantly more impaired in both outcome measures than those injured at 0.5 mm (p < 0.05). The cortical lesion increased in size between 24 h and 7 days in both injury groups, but was significantly larger in the 1.0 mm group. Hippocampal cell loss was observed in the hilar and CA3 regions in both groups, and in the CA1 and dentate granule cell layers in the 1.0 mm group. Regional patterns of IgG extravasation and reactive astrocytosis were similar in the two injured groups, but changes were more persistent in the 1.0 mm group. Both levels of injury resulted in acute loss of neuronal MAP-2 immunoreactivity in the cortex and sub-region specific changes in the hippocampus. Thus, increasing the depth of impact led to similar structural alterations in neurons, astrocytes and the vasculature, but resulted in greater behavioral deficits and cortical and hippocampal cell death.

Original languageEnglish
Pages (from-to)1241-1253
Number of pages13
JournalJournal of Neurotrauma
Volume23
Issue number8
DOIs
StatePublished - Aug 2006

Keywords

  • Blood-brain barrier
  • Cognition
  • Contusion
  • MAP-2
  • Motor function
  • Reactive astrocytes
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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