Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood–brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6–72 h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray–white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion.

尽管脑震荡现在被认为是主要的健康问题，但其非致死性质限制了其潜在病理生理学特征。特别是，潜在的神经病理学改变通常是从非侵入性技术或严重创伤性脑损伤（TBI）的验尸检查中推断出来的。在这里，我们使用了基于人类脑震荡的猪头部旋转加速度猪模型，以检查弥漫性轴索损伤和神经胶质反应与损伤后的血脑屏障（BBB）完整性。然后，我们通过与可能进行死后检查的人类严重TBI的病理变化进行比较，确定了猪脑震荡发现的潜在临床意义。猪受伤后6-72小时，我们观察到BBB的多灶性破坏，其表现为血清蛋白的外渗，纤维蛋白原和免疫球蛋白-G，无出血或其他局灶性病变。在与生物力学侮辱相一致的定型分布中观察到了血脑屏障破坏。特别是，经常在具有不同物质特性的组织区域之间的界面处观察到渗出的血清蛋白，包括灰白色边界，脑室周围和脑膜下区域。此外，在白质中，BBB破坏与轴突病理区域存在大量重叠。星形胶质细胞（GFAP阳性）和神经元（MAP-2阳性）中小分子胶质细胞（IBA1阳性）中，血液中蛋白的急性血管周摄取明显。对人严重TBI的并行检查发现，血清外渗和胶质细胞摄取血清蛋白的模式相似，但其程度要比猪模型高得多，这归因于较高的损伤严重程度。这些数据表明，血脑屏障破坏代表了脑震荡的一种新的重要病理特征。