Reeves Thomas M, Phillips Linda L, Povlishock John T
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, 1217 E. Marshall Street, Room 740, MCV Campus Box 980709, Richmond, VA 23298, USA.
Exp Neurol. 2005 Nov;196(1):126-37. doi: 10.1016/j.expneurol.2005.07.014. Epub 2005 Aug 18.
Traumatic axonal injury (TAI), a common feature of traumatic brain injury, is associated with postinjury morbidity and mortality. However, TAI is not uniformly expressed in all axonal populations, with fiber caliber and anatomical location influencing specific TAI pathology. To study differential axonal vulnerability to brain injury, axonal excitability and integrity were assessed in the corpus callosum following fluid percussion injury in the rat. In brain slice electrophysiological recordings, compound action potentials (CAPs) were evoked in the corpus callosum, and injury effects were quantified separately for CAP waveform components generated by myelinated axons (N1 wave) and by unmyelinated axons (N2 wave). Ultrastructural analyses were also conducted of TAI-induced morphological changes in these axonal populations. The two populations of axons differed in response to brain injury, and in their functional recovery, during the first week postinjury. Amplitudes of N1 and N2 were significantly depressed at 3 h, 1 day, and 3 days survival. N1 amplitudes exhibited a recovery to control levels by 7 days postinjury. In contrast, N2 amplitudes were persistently suppressed through 7 days postinjury. Strength-duration properties of evoked CAPs further differentiated the effects of injury in these axonal populations, with N2 exhibiting an elevated strength-duration time constant postinjury. Ultrastructural observations revealed degeneration of myelinated axons consistent with diffuse injury sequelae, as well as previously undocumented pathology within the unmyelinated fiber population. Collectively, these findings demonstrate differential vulnerabilities of axons to brain injury and suggest that damage to unmyelinated fibers may play a significant role in morbidity associated with brain injury.
创伤性轴突损伤（TAI）是创伤性脑损伤的一个常见特征，与伤后发病率和死亡率相关。然而，TAI在所有轴突群体中并非均匀表达，纤维直径和解剖位置会影响特定的TAI病理变化。为了研究轴突对脑损伤的不同易损性，在大鼠液压冲击伤后评估了胼胝体中的轴突兴奋性和完整性。在脑片电生理记录中，在胼胝体中诱发复合动作电位（CAPs），并分别对由有髓轴突（N1波）和无髓轴突（N2波）产生的CAP波形成分的损伤效应进行量化。还对这些轴突群体中TAI诱导的形态学变化进行了超微结构分析。在伤后的第一周，这两种轴突群体对脑损伤的反应及其功能恢复情况有所不同。在伤后3小时、1天和3天存活时，N1和N2的振幅显著降低。伤后7天，N1振幅恢复到对照水平。相比之下，N2振幅在伤后7天一直受到抑制。诱发CAPs的强度-时间特性进一步区分了这些轴突群体中的损伤效应，伤后N2的强度-时间常数升高。超微结构观察显示有髓轴突变性与弥漫性损伤后遗症一致，以及在无髓纤维群体中存在以前未记录的病理变化。总的来说，这些发现证明了轴突对脑损伤的不同易损性，并表明无髓纤维的损伤可能在与脑损伤相关的发病率中起重要作用。
