Graded model of diffuse axonal injury for studying head injury‐induced cognitive dysfunction in rats
Graded model of diffuse axonal injury for studying head injury‐induced cognitive dysfunction in rats
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DOI：
10.1111/j.1440-1789.2008.00956.x
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发表时间：
2009-04
期刊：
影响因子：
2.3
通讯作者：
Katsuhiko Maruichi;S. Kuroda;Y. Chiba;Masaaki Hokari;H. Shichinohe;K. Hida;Y. Iwasaki
中科院分区：
文献类型：
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作者：
Katsuhiko Maruichi;S. Kuroda;Y. Chiba;Masaaki Hokari;H. Shichinohe;K. Hida;Y. Iwasaki
弥漫性轴索损伤（DAI）在闭合性脑损伤后患者的认知功能障碍、情绪困难和行为障碍的发展中起着重要作用，即使他们在常规MRI上没有明确的异常。本研究旨在开发一种高度受控和可重现的DAI模型，模拟人类创伤后认知功能障碍。Sprague-道利（SD）大鼠遭受冲击加速度头部损伤，使用气动冲击靶向位于其颅骨中心的钢盘。受伤的严重程度分为三个级别，通过调整驱动压力在60，70或80磅每平方英寸。在损伤后2天获得体内MRI。在损伤后1周和2周使用Morris水迷宫评价认知功能。2周后行HE染色和免疫组化观察神经元和轴突损伤情况。MRI证实该模型在脑中未引起大体结构改变。认知功能障碍的程度和持续时间取决于撞击力。组织学分析显示新皮质中神经元和微管相关蛋白2阳性轴突的力依赖性损伤。海马损伤不太明显，与认知功能障碍无关。这是第一份报告，准确地评估阈值的冲击能量，导致新皮层损伤和认知功能障碍的啮齿动物。该模型适用于阐明创伤后脑损伤的复杂机制，并测试针对弥漫性轴突损伤所致创伤后认知功能障碍的新治疗方法。
Diffuse axonal injury (DAI) plays a major role in the development of cognitive dysfunction, emotional difficulties and behavioral disturbances in patients following closed head injury, even when they have no definite abnormalities on conventional MRI. This study aimed to develop a highly controlled and reproducible model for DAI that simulates post‐traumatic cognitive dysfunction in humans. Sprague‐Dawley (SD) rats were subjected to impact acceleration head injury, using a pneumatic impact targeted to a steel disc centered onto their skull. The severity of injury was graded as three levels by adjusting the driving pressure at 60, 70 or 80 pounds per square inch. In vivo MRI was obtained 2 days post‐injury. Cognitive function was evaluated using the Morris water maze at 1 and 2 weeks post‐injury. HE staining and immunohistochemistry were performed to assess neuronal and axonal damages after 2 weeks. MRI demonstrated that this model induced no gross structural modification in the brain. The degree and duration of cognitive dysfunction were dependent on the force of impact. Histological analysis revealed the force‐dependent damage of the neurons and microtubule‐associated protein 2‐positive axons in the neocortex. Hippocampal damage was much less pronounced and was not linked to cognitive dysfunction. This is the first report that precisely evaluates the threshold of impact energy to lead to neocortical damage and cognitive dysfunction in rodents. This model would be suitable for clarifying the complex mechanisms of post‐traumatic brain damage and testing novel therapeutic approaches against post‐traumatic cognitive dysfunction due to diffuse axonal damage.