Ojo Joseph O, Bachmeier Corbin, Mouzon Benoit C, Tzekov Radouil, Mullan Michael, Davies Heather, Stewart Michael G, Crawford Fiona
From the Roskamp Institute, Neuropathology Department, Sarasota, Florida (JOO, CB, BCM, RT, MM, FC); Open University, Life Science Department, Walton Hall, Milton Keynes, London, United Kingdom (HD, MGS); and James A. Haley Hospital, Tampa, Florida (BCM, RT, FC).
J Neuropathol Exp Neurol. 2015 Oct;74(10):1012-35. doi: 10.1097/NEN.0000000000000247.
Mild traumatic brain injury is a risk factor for neurodegenerative disease. We recently developed a model of repetitive concussive injury in mice that we have extensively characterized from 24 hours to 24 months after injury. Animals show evidence of progressive spatial memory deficits, thinning of the corpus callosum, axonal injury, and neuroglial activation. Here, we extended our neuropathologic characterization to the ultrastructural level in both a qualitative and a quantitative study. We focused on chronic (3 and 6 months) postinjury time points when the earliest stages of degenerative secondary changes were previously observed. In both C57BL/6 and hTau mice, we found white matter damage typified by axonal degeneration, microglial phagocytosis, and increased neuroglial cell density. In the cerebral cortex, we observed evidence of synaptic degeneration, dark neurons, altered dendritic microfilaments, subtle changes to the microvasculature, a mild augmentation of age-related features such as lipofuscin deposition, and electron-dense inclusions in microglial and perivascular cells. The majority of these ultrastructural features seemed to be more prominent at 3 versus 6 months after injury. Similar patterns were observed in C57BL/6 and hTau mice. These findings further support the relevance of our concussive injury model to the consequences of repetitive mild traumatic brain injury in humans.
轻度创伤性脑损伤是神经退行性疾病的一个风险因素。我们最近在小鼠中建立了一种重复性脑震荡损伤模型，并在损伤后24小时至24个月对其进行了广泛的特征描述。动物表现出进行性空间记忆缺陷、胼胝体变薄、轴突损伤和神经胶质激活的证据。在此，我们在一项定性和定量研究中将神经病理学特征扩展到超微结构水平。我们关注损伤后慢性期（3个月和6个月）的时间点，此前已观察到退行性继发性变化的最早阶段。在C57BL/6小鼠和hTau小鼠中，我们都发现了以轴突变性、小胶质细胞吞噬作用和神经胶质细胞密度增加为特征的白质损伤。在大脑皮层，我们观察到突触变性、暗神经元、树突微丝改变、微血管的细微变化、脂褐素沉积等与年龄相关特征的轻度增加以及小胶质细胞和血管周围细胞中的电子致密包涵体的证据。这些超微结构特征中的大多数在损伤后3个月比6个月似乎更明显。在C57BL/6小鼠和hTau小鼠中观察到类似的模式。这些发现进一步支持了我们的脑震荡损伤模型与人类重复性轻度创伤性脑损伤后果的相关性。
