Program in Neuroscience, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
J Neurotrauma. 2011 Apr;28(4):547-63. doi: 10.1089/neu.2010.1729.
Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function.
脑震荡性脑损伤（CBI）约占美国每年所有脑损伤患者的 75%，尤其在接触性运动中较为常见。脑震荡是弥漫性创伤性脑损伤（TBI）最轻微的形式，导致短暂的认知功能障碍，其神经病理学基础是创伤性轴索损伤（TAI）。为了评估与脑震荡引起的认知缺陷相关的结构和功能变化，成年小鼠的完整颅骨中线处受到撞击，导致短暂的呼吸暂停期和翻正反射丧失。闭合性颅脑损伤也导致皮质的湿重：干重比增加，提示在 24 小时内出现水肿，伤后 3 天内皮质和海马齿状回出现 Fluoro-Jade-B 标记的变性神经元。与假损伤小鼠相比，脑损伤小鼠在伤后第 1 天至第 3 天使用 Morris 水迷宫测量时，空间获取和工作记忆明显受损（p<0.001），但在伤后第 4 天之后没有这种情况。在损伤后第 1 天和第 3 天，胼胝体和扣带回的内轴突中淀粉样前体蛋白的积累伴随着神经丝去磷酸化、Fluoro-Gold 和突触小体蛋白的转运受损以及轴突传导功能障碍。重要的是，直到伤后 14 天，逆行转运和有髓轴突动作电位的缺陷仍持续存在，此时出现轴突变性。这些数据表明，尽管急性认知缺陷得到恢复，但脑震荡性脑外伤导致轴突变性和轴突功能持续紊乱。
