Apoptotic and behavioral sequelae of mild brain trauma in mice.
Apoptotic and behavioral sequelae of mild brain trauma in mice.
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小鼠轻度脑损伤的细胞凋亡和行为后遗症。
DOI：
10.1002/jnr.21160
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发表时间：
2007
影响因子：
4.2
通讯作者：
Greig,NigelH
中科院分区：
文献类型：
--
作者：
Tweedie,David;Milman,Anat;Holloway,HaroldW;Li,Yazhou;Harvey,BrandonK;Shen,Hui;Pistell,PaulJ;Lahiri,DebomoyK;Hoffer,BarryJ;Wang,Yun;Pick,ChaimG;Greig,NigelH
轻度创伤性脑损伤（mTBI）在青少年和年轻人中并不罕见。虽然它不会导致明显的脑形态缺陷，但它与长期的认知、情绪和行为问题有关。在此，我们描述了与实验性mTBI相关的小鼠生化和行为变化，这些变化可能作为介入治疗的靶点或替代标记物。具体来说，通过体重下降30 - g和50 - g诱导mTBI，在8和72小时后，通过Western blot分析，在与影响同侧的海马中量化细胞凋亡标志物- caspase - 3， Bax，凋亡诱导因子（AIF）和细胞色素c （Cyt - c）。我们还测量了淀粉样蛋白β前体蛋白（APP）的水平，并进行了特定的行为测试——被动回避、开放领域和强迫游泳（Porsolt）范式——来评估学习、情绪和情绪记忆。在没有出血或梗死的情况下，通过三苯四唑氯染色评估，在两次mTBI后，procaspase‐3和Bax水平明显改变。未检测到裂解的caspase - 3，并且在72小时时AIF和Cyt - c水平发生显著变化，但APP未发生显著变化。mTBI小鼠在1小时和24小时的神经学检查以及在72小时的被动回避/开放领域检查中与对照组无法区分，但在强迫游泳范式中可以区分。总的来说，该模型模拟了mTBI对与人类状况相关的脑功能的扩散效应，并强调了特定的凋亡蛋白和行为范式，作为前瞻性干预策略的潜在标记。©2007 Wiley‐Liss, Inc。
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.