David Tweedie and Anat Milman contributed equally to this work as first authors.
Apoptotic and behavioral sequelae of mild brain trauma in mice
Article first published online: 22 JAN 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 85, Issue 4, pages 805–815, March 2007
How to Cite
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. and Greig, N. H. (2007), Apoptotic and behavioral sequelae of mild brain trauma in mice. J. Neurosci. Res., 85: 805–815. doi: 10.1002/jnr.21160
- Issue published online: 14 FEB 2007
- Article first published online: 22 JAN 2007
- Manuscript Revised: 30 OCT 2006
- Manuscript Accepted: 30 OCT 2006
- Manuscript Received: 17 AUG 2006
- Intramural Research Programs of the National Institute on Aging and National Institute on Drug Abuse, National Institutes of Health
- National Institutes of Health. Grant Number: R01AG023055 (to D.K.L.)
- traumatic brain injury;
- mild (mTBI);
- amyloid-β precursor protein;
- apoptosis inducing factor (AIF);
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. © 2007 Wiley-Liss, Inc.