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Apoptotic and behavioral sequelae of mild brain trauma in mice
Author(s) -
Tweedie David,
Milman Anat,
Holloway Harold W.,
Li Yazhou,
Harvey Brandon K.,
Shen Hui,
Pistell Paul J.,
Lahiri Debomoy K.,
Hoffer Barry J.,
Wang Yun,
Pick Chaim G.,
Greig Nigel H.
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21160
Subject(s) - apoptosis , traumatic brain injury , open field , medicine , hippocampus , cytochrome c , neuroscience , psychology , pathology , biology , psychiatry , biochemistry
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.