Apoptotic and behavioral sequelae of mild brain trauma in mice

David Tweedie, Anat Milman, Harold W. Holloway, Yazhou Li, Brandon K. Harvey, Hui Shen, Paul J. Pistell, Debomoy K. Lahiri, Barry J. Hoffer, Yun Wang, Chaim G. Pick, Nigel H. Greig

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Mild traumatic brain injury (mTBI) is a not uncommon event in adolescents and young adults. Although it does not result in clear morphological brain defects, it is associated with long-term cognitive, emotional, and behavioral problems. Herein, we characterized the biochemical and behavioral changes associated with experimental mTBI in mice that may act as either targets or surrogate markers for interventional therapy. Specifically, mTBI was induced by 30-g and 50-g weight drop, and at 8 and 72 hr thereafter markers of cellular apoptosis - caspase-3, Bax, apoptosis-inducing factor (AIF), and cytochrome-c (Cyt-c) - were quantified by Western blot analysis in hippocampus ipsilateral to the impact. Levels of amyloid-β precursor protein (APP) were also measured, and specific behavioral tests-passive avoidance, open field, and forced swimming (Porsolt) paradigms - were undertaken to assess learning, emotionality, and emotional memory. In the absence of hemorrhage or infarcts, as assessed by triphenyltetrazolium chloride staining, procaspase-3 and Bax levels were markedly altered following mTBI at both times. No cleaved caspase-3 was detected, and levels of AIF and Cyt-c, but not APP, were significantly changed at 72 hr. Mice subjected to mTBI were indistinguishable from controls by neurological examination at 1 and 24 hr, and by passive avoidance/ open field at 72 hr, but could be differentiated in the forced swimming paradigm. In general, this model mimics the diffuse effects of mTBI on brain function associated with the human condition and highlights specific apoptotic proteins and a behavioral paradigm as potential markers for prospective interventional strategies.

Original languageEnglish (US)
Pages (from-to)805-815
Number of pages11
JournalJournal of Neuroscience Research
Volume85
Issue number4
DOIs
StatePublished - Mar 1 2007

Keywords

  • Amyloid-β precursor protein
  • Apoptosis
  • Apoptosis inducing factor (AIF)
  • Bax
  • Cytochrome-c
  • Mild (mTBI)
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Tweedie, D., Milman, A., Holloway, H. W., Li, Y., Harvey, B. K., Shen, H., Pistell, P. J., Lahiri, D. K., Hoffer, B. J., Wang, Y., Pick, C. G., & Greig, N. H. (2007). Apoptotic and behavioral sequelae of mild brain trauma in mice. Journal of Neuroscience Research, 85(4), 805-815. https://doi.org/10.1002/jnr.21160