Concussive Brain Trauma in the Mouse Results in Acute Cognitive Deficits and Sustained Impairment of Axonal Function
Concussive Brain Trauma in the Mouse Results in Acute Cognitive Deficits and Sustained Impairment of Axonal Function
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DOI：
10.1089/neu.2010.1729
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Raghupathi, Ramesh
中科院分区：
文献类型：
--
作者：
Creed, Jennifer A.;DiLeonardi, Ann Mae;Raghupathi, Ramesh
脑震荡（CBI）每年约占美国所有脑损伤患者的75%，在接触性运动中尤为普遍。脑震荡是弥漫性创伤性脑损伤（TBI）中最轻微的一种，可导致短暂性认知功能障碍，其神经病理学基础是创伤性轴索损伤（TAI）。为了评估与脑震荡诱导的认知缺陷相关的结构和功能变化，成年小鼠在中线缝合处受到完整颅骨的撞击，导致短暂的呼吸暂停和翻正反射的丧失。闭合性头部损伤也导致在湿重：干重比在皮质中的水肿，在第一个24小时内，和外观的Fluoro-Jade-B-标记的变性神经元在皮层和海马齿状回内的前3天损伤后的增加。与假损伤小鼠相比，脑损伤小鼠在前3天内使用Morris水迷宫测量时表现出空间获取和工作记忆的显著缺陷（p < 0.001），但在损伤后第4天后没有。在损伤后1天和3天，胼胝体和扣带回中淀粉样前体蛋白的轴突内积累伴随着神经丝去磷酸化、Fluoro-Gold和突触素的运输受损以及轴突电导的缺陷。重要的是，逆行运输和有髓轴突动作电位的缺陷持续观察到损伤后14天，此时轴突变性明显。这些数据表明，尽管从急性认知缺陷中恢复，脑震荡创伤仍会导致轴突变性和轴突功能的持续干扰。
Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight: dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p < 0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function.