Repeated mild traumatic brain injury results in long-term white-matter disruption
Repeated mild traumatic brain injury results in long-term white-matter disruption
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DOI：
10.1038/jcbfm.2014.6
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发表时间：
2014-04-01
影响因子：
6.3
通讯作者：
Obenaus, Andre
中科院分区：
文献类型：
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作者：
Donovan, Virginia;Kim, Claudia;Obenaus, Andre
轻度创伤性脑损伤（mTBI）是一个日益关注的公共卫生问题，因为重复性损伤可加重现有的神经病理学并导致更多的神经功能缺陷。与其他重复性mTBI （rmTBI）模型相比，我们的研究重点是双侧mTBI诱导间隔7天后的长期白质异常。采用控制性皮质冲击（CCI）诱导单纯性和rmTBI大鼠的右侧皮质发生初始mTBI，随后对rmTBI动物的左侧皮质进行第二次损伤。沙姆斯只接受了颅骨切除术。损伤后60天对胼胝体前体进行体外弥散张量成像（DTI）、透射电镜（TEM）和组织学检查。rmTBI动物双侧径向弥散性（髓鞘）显著增加，而两组间轴向弥散性（轴突）变化不大。此外，TEM显示rmTBI组除了髓鞘异常外，还显示g比和轴突直径增加。我们的DTI结果显示髓磷脂持续变化，而TEM数据显示rmTBI后60天轴突持续变化。这些数据表明，双侧rmTBI相隔7天导致白质进行性改变，而单次mTBI后未观察到这种改变。
Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.