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大鼠轻度创伤性脑损伤改变边缘系统的神经元数量,并增加条件性恐惧和焦虑样行为。

Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors.

机构信息

Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.

出版信息

Exp Neurol. 2012 Jun;235(2):574-87. doi: 10.1016/j.expneurol.2012.03.012. Epub 2012 Apr 1.

DOI:10.1016/j.expneurol.2012.03.012
PMID:22498103
Abstract

Recent reports suggest that experiencing a mild closed head trauma or mild traumatic brain injury (mTBI) is associated with a greater incidence of anxiety disorders. Dysfunction of limbic structures, such as the medial prefrontal cortex, amygdala and hippocampus, is associated with the symptoms of anxiety disorders. Therefore, the goal of the current studies was to characterize the consequences of closed mTBI on these limbic structures and associated fear and anxiety-related behaviors. A weight-drop procedure was employed to induce mTBI in male rats. Rats were transcardically perfused 4 or 9 days following exposure to mTBI or control procedures, and neuronal number, brain region area, and the number of apoptotic cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and acquisition, retention and extinction of contextual fear were also assessed. Findings suggest that mTBI was associated with significant neuronal cell loss in the CA1 region of the dorsal hippocampus and increased cell number in subregions of the amygdala, both of which appear to be related to alterations to apoptosis in these regions following mTBI. Furthermore, mTBI increased expression of anxiety-like behaviors and conditioned fear, with no effect on motor performance or nociception. Overall, a single impact to the skull to mimic mTBI in rats produces discrete alterations to neuronal numbers within the limbic system and specific emotional deficits, providing a potential neurobiological link between mTBI and anxiety disorders.

摘要

最近的报告表明,轻度闭合性颅脑外伤或轻度创伤性脑损伤(mTBI)与焦虑障碍的发生率增加有关。边缘结构(如内侧前额叶皮层、杏仁核和海马体)的功能障碍与焦虑障碍的症状有关。因此,当前研究的目标是描述闭合性 mTBI 对这些边缘结构以及相关的恐惧和焦虑相关行为的影响。采用重物坠落程序诱导雄性大鼠 mTBI。在 mTBI 或对照程序暴露后 4 或 9 天,对大鼠进行心脏灌注,然后确定每个区域的神经元数量、脑区面积和凋亡细胞数量。在另一组大鼠中,还评估了 mTBI 对焦虑样行为、运动功能、痛觉和情境恐惧的获得、保持和消退的影响。研究结果表明,mTBI 与背侧海马 CA1 区的神经元细胞大量丢失以及杏仁核亚区的细胞数量增加有关,这两者似乎都与 mTBI 后这些区域的凋亡改变有关。此外,mTBI 增加了焦虑样行为和条件性恐惧的表达,而对运动表现或痛觉没有影响。总之,模拟大鼠 mTBI 的颅骨单次冲击会导致边缘系统内神经元数量发生离散变化,并出现特定的情绪缺陷,为 mTBI 与焦虑障碍之间提供了潜在的神经生物学联系。

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