Repeated Traumatic Brain Injury Affects Composite Cognitive Function in Piglets
Repeated Traumatic Brain Injury Affects Composite Cognitive Function in Piglets
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DOI：
10.1089/neu.2008.0845
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发表时间：
2009-07-01
影响因子：
4.2
通讯作者：
Margulies, Susan S.
中科院分区：
文献类型：
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作者：
Friess, Stuart H.;Ichord, Rebecca N.;Margulies, Susan S.
重复性轻度头部损伤对儿科人群的累积影响尚不清楚。我们开发了一种认知综合功能障碍评分，将新生仔猪的白质损伤严重程度与执行功能、记忆、学习和问题解决的神经行为评估相关联。对麻醉的 3 至 5 天龄仔猪进行单次（n = 7）、两次相隔一天（n = 7）和两次相隔一周（n = 7）头部的中等（190 rad/s）快速非冲击轴向旋转，并与器械假手术（n = 7）进行比较。与其他组相比，相隔一天经历两次头部旋转的动物的死亡率（43%）显着更高，并且与仪器假手术相比，在基于视觉的问题解决方面的失败率更高。通过β-APP染色评估，相隔一周的两次损伤组的白质损伤明显高于单次损伤和假手术组。认知综合评分的恶化与白质轴突损伤严重程度的增加密切相关。在我们未成熟的 TBI 大型动物模型中，根据神经病理学和神经行为功能结果评估，与单次头部旋转相比，两次头部旋转产生的结果较差。更重要的是，我们观察到，与相隔 7 天相比，相隔 24 小时进行头部旋转时，损伤严重程度和死亡率有所增加。这些观察结果对于遭受反复头部创伤的婴儿具有重要的临床意义。
Cumulative effects of repetitive mild head injury in the pediatric population are unknown. We have developed a cognitive composite dysfunction score that correlates white matter injury severity in neonatal piglets with neurobehavioral assessments of executive function, memory, learning, and problem solving. Anesthetized 3- to 5-day-old piglets were subjected to single (n=7), double one day apart (n=7), and double one week apart (n=7) moderate (190 rad/s) rapid non-impact axial rotations of the head and compared to instrumented shams (n=7). Animals experiencing two head rotations one day apart had a significantly higher mortality rate (43%) compared to the other groups and had higher failures rates in visual-based problem solving compared to instrumented shams. White matter injury, assessed by beta-APP staining, was significantly higher in the double one week apart group compared to that with single injury and sham. Worsening performance on cognitive composite score correlated well with increasing severity of white matter axonal injury. In our immature large animal model of TBI, two head rotations produced poorer outcome as assessed by neuropathology and neurobehavioral functional outcomes compared to that with single rotations. More importantly, we have observed an increase in injury severity and mortality when the head rotations occur 24 h apart compared to 7 days apart. These observations have important clinical translation to infants subjected to repeated inflicted head trauma.