Pierce J E, Smith D H, Trojanowski J Q, McIntosh T K
Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Neuroscience. 1998 Nov;87(2):359-69. doi: 10.1016/s0306-4522(98)00142-0.
Clinical studies have demonstrated that patients sustain prolonged behavioral deficits following traumatic brain injury, in some cases culminating in the cognitive and histopathological hallmarks of Alzheimer's disease. However, few studies have examined the long-term consequences of experimental traumatic brain injury. In the present study, anesthetized male Sprague-Dawley rats (n = 185) were subjected to severe lateral fluid-percussion brain injury (n = 115) or sham injury (n = 70) and evaluated up to one year post-injury for cognitive and neurological deficits and histopathological changes. Compared with sham-injured controls, brain-injured animals showed a spatial learning impairment that persisted up to one year post-injury. In addition, deficits in specific neurologic motor function tasks also persisted up to one year post-injury. Immunohistochemistry using multiple antibodies to the amyloid precursor protein and/or amyloid precursor protein-like proteins revealed novel axonal degeneration in the striatum, corpus callosum and injured cortex up to one year post-injury and in the thalamus up to six months post-injury. Histologic evaluation of injured brains demonstrated a progressive expansion of the cortical cavity, enlargement of the lateral ventricles, deformation of the hippocampus, and thalamic calcifications. Taken together, these findings indicate that experimental traumatic brain injury can cause long-term cognitive and neurologic motor dysfunction accompanied by continuing neurodegeneration.
临床研究表明，创伤性脑损伤患者会出现长期行为缺陷，在某些情况下，最终会出现阿尔茨海默病的认知和组织病理学特征。然而，很少有研究探讨实验性创伤性脑损伤的长期后果。在本研究中，对185只麻醉的雄性Sprague-Dawley大鼠进行了实验，其中115只遭受严重的侧方流体冲击性脑损伤，70只进行假手术，并在损伤后长达一年的时间里评估其认知、神经功能缺陷和组织病理学变化。与假手术对照组相比，脑损伤动物表现出空间学习障碍，这种障碍在损伤后持续长达一年。此外，特定神经运动功能任务的缺陷在损伤后也持续长达一年。使用多种针对淀粉样前体蛋白和/或淀粉样前体蛋白样蛋白的抗体进行免疫组织化学分析显示，在损伤后长达一年的时间里，纹状体、胼胝体和损伤皮层出现了新的轴突变性，在损伤后长达六个月的时间里，丘脑也出现了轴突变性。对损伤大脑的组织学评估显示，皮质腔逐渐扩大、侧脑室增大、海马体变形以及丘脑钙化。综上所述，这些发现表明，实验性创伤性脑损伤可导致长期的认知和神经运动功能障碍，并伴有持续的神经退行性变。
