Maruichi Katsuhiko, Kuroda Satoshi, Chiba Yasuhiro, Hokari Masaaki, Shichinohe Hideo, Hida Kazutoshi, Iwasaki Yoshinobu
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Neuropathology. 2009 Apr;29(2):132-9. doi: 10.1111/j.1440-1789.2008.00956.x. Epub 2008 Aug 13.
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.
弥漫性轴索损伤（DAI）在闭合性颅脑损伤患者认知功能障碍、情感障碍和行为紊乱的发生中起主要作用，即使他们在传统磁共振成像（MRI）上没有明确异常。本研究旨在建立一种高度可控且可重复的DAI模型，以模拟人类创伤后认知功能障碍。将Sprague-Dawley（SD）大鼠进行冲击加速性颅脑损伤，使用气动冲击装置，将冲击目标对准其颅骨中心的钢盘。通过将驱动压力调整为每平方英寸60、70或80磅，将损伤严重程度分为三个等级。在损伤后2天进行活体MRI检查。在损伤后1周和2周使用莫里斯水迷宫评估认知功能。在2周后进行苏木精-伊红（HE）染色和免疫组织化学检查，以评估神经元和轴突损伤。MRI显示该模型未引起大脑明显的结构改变。认知功能障碍的程度和持续时间取决于冲击力度。组织学分析显示，新皮质中神经元和微管相关蛋白2阳性轴突的损伤与冲击力度有关。海马损伤则不那么明显，且与认知功能障碍无关。这是第一份精确评估导致啮齿动物新皮质损伤和认知功能障碍的冲击能量阈值的报告。该模型将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索损伤所致创伤后认知功能障碍的新型治疗方法。
