Department of Neurosurgery, No.3 People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Neuroscience. 2010 Aug 11;169(1):357-69. doi: 10.1016/j.neuroscience.2010.04.075. Epub 2010 May 6.
Diffuse axonal injury (DAI) is one of the most common and important pathologic features of human traumatic brain injury (TBI), accounting for high mortality and development of persistent post-traumatic neurologic sequelae. Although a relatively high number of therapies have been shown to be effective in experimental models, there are currently few treatments that are effective for improving the prognosis of clinical DAI. A major reason is the failure of current models to validly reproduce the pathophysiological characteristics observed after clinical DAI. In the present study, we employed a specially designed, highly controllable model to induce a sudden rotation in the coronal plane (75 degrees rotation at 1.6x10(4) degrees/s) combined with lateral translation (1.57 cm displacement at 3.4x10(2) cm/s) to the rat's head. We were interested in discovering whether the combined accelerations could reproduce the pathophysiological changes analogous to those seen in human DAI. The axonal injury as assessed with amyloid protein precursor (APP) as a marker was consistently present in all injured rats. The commonly injured brain regions included the subcortical regions, deep white matter, corpus callosum and brain stem. The evolution of APP accumulations in brain sections depicted the detailed progression of axonal pathology. Ultrastructural studies gave further insights into the presence and progression of axonal injury. All injured rats exhibited transient physiological dysfunction, as well as immediate and dramatic neurological impairment that still persisted at 14 days after injury. These results suggest that this model reproduced the major pathophysiological changes analogous to those observed after severe clinical TBI and provides an attractive vehicle for experimental brain injury research.
弥漫性轴索损伤（DAI）是人类创伤性脑损伤（TBI）中最常见和最重要的病理特征之一，占高死亡率和持续创伤后神经后遗症的发展。尽管有相当数量的治疗方法在实验模型中被证明是有效的，但目前很少有治疗方法能有效地改善临床 DAI 的预后。主要原因是当前模型未能有效地复制临床 DAI 后观察到的病理生理特征。在本研究中，我们采用了一种特别设计的、高度可控的模型，使大鼠头部突然在冠状面旋转（75 度旋转，角速度为 1.6x10(4)度/秒），同时伴有侧向平移（1.57 厘米位移，速度为 3.4x10(2)厘米/秒）。我们感兴趣的是发现这种联合加速度是否能复制类似于人类 DAI 所见的病理生理变化。用淀粉样蛋白前体（APP）作为标志物评估的轴索损伤在所有受伤的大鼠中始终存在。常见的受伤脑区包括皮质下区域、深部白质、胼胝体和脑干。脑切片中 APP 积累的演变描绘了轴索病理学的详细进展。超微结构研究进一步揭示了轴索损伤的存在和进展。所有受伤的大鼠均表现出短暂的生理功能障碍，以及立即和显著的神经功能障碍，在受伤后 14 天仍持续存在。这些结果表明，该模型复制了类似于严重临床 TBI 后观察到的主要病理生理变化，并为实验性脑损伤研究提供了一个有吸引力的载体。
