Smith D H, Chen X H, Nonaka M, Trojanowski J Q, Lee V M, Saatman K E, Leoni M J, Xu B N, Wolf J A, Meaney D F
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
J Neuropathol Exp Neurol. 1999 Sep;58(9):982-92. doi: 10.1097/00005072-199909000-00008.
Brain trauma in humans increases the risk for developing Alzheimer disease (AD) and may induce the acute formation of AD-like plaques containing amyloid beta (A beta). To further explore the potential link between brain trauma and neurodegeneration, we conducted neuropathological studies using a pig model of diffuse brain injury. Brain injury was induced in anesthetized animals via nonimpact head rotational acceleration of 110 degrees over 20 ms in the coronal plane (n = 15 injured, n = 3 noninjured). At 1, 3, 7, and 10 days post-trauma, control and injured animals were euthanized and immunohistochemical analysis was performed on brain sections using antibodies specific for A beta, beta-amyloid precursor protein (betaPP), tau, and neurofilament (NF) proteins. In addition to diffuse axonal pathology, we detected accumulation of A beta and tau that colocalized with immunoreactive betaPP and NF in damaged axons throughout the white matter in all injured animals at 3-10 days post-trauma. In a subset of brain injured animals, diffuse A beta-containing plaque-like profiles were found in both the gray and white matter, and accumulations of tau and NF rich inclusions were observed in neuronal perikarya. These results show that this pig model of diffuse brain injury is characterized by accumulations of proteins that also form pathological aggregates in AD and related neurodegenerative diseases.
人类脑外伤会增加患阿尔茨海默病（AD）的风险，并可能诱导急性形成含有β-淀粉样蛋白（Aβ）的AD样斑块。为了进一步探索脑外伤与神经退行性变之间的潜在联系，我们使用弥漫性脑损伤的猪模型进行了神经病理学研究。通过在冠状平面上20毫秒内110度的非撞击头部旋转加速，在麻醉动物中诱导脑损伤（n = 15只受伤，n = 3只未受伤）。在创伤后1、3、7和10天，对对照动物和受伤动物实施安乐死，并使用针对Aβ、β-淀粉样前体蛋白（βPP）、tau和神经丝（NF）蛋白的抗体对脑切片进行免疫组织化学分析。除了弥漫性轴突病理学改变外，我们在创伤后3 - 10天的所有受伤动物的整个白质受损轴突中检测到Aβ和tau的积累，它们与免疫反应性βPP和NF共定位。在一部分脑损伤动物中，在灰质和白质中均发现了弥漫性含Aβ的斑块样结构，并且在神经元胞体中观察到tau和富含NF的包涵体的积累。这些结果表明，这种弥漫性脑损伤的猪模型的特征是蛋白质的积累，而这些蛋白质在AD及相关神经退行性疾病中也会形成病理性聚集体。
