Povlishock J T, Marmarou A, McIntosh T, Trojanowski J Q, Moroi J
Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0709, USA.
J Neuropathol Exp Neurol. 1997 Apr;56(4):347-59.
Recently we reported that traumatic brain injury evokes local changes in the axolemma's permeability, in concert with local cytoskeletal changes involving neurofilament (NF) compaction and sidearm loss, all of which contribute to the genesis of reactive axonal change. Since it was of concern that these events may be either injury model- or species-specific, we sought to address these phenomena in a different but well-characterized animal model and species. Further, to provide more compelling insight into the potential for NF compaction and sidearm alteration, we also employed antibodies specific for the NF rod domains, which are readily visualized only when the NF sidearms are disturbed. Rats were subjected to impact acceleration injury. To assess the potential for altered axolemmal permeability, 5 animals received intrathecal horseradish peroxidase (HRP), normally excluded by the intact axolemma. To assess the potential for NF sidearm alteration, another 14 animals were processed for the visualization of antibodies targeting the NF rod domain at 5 minutes (min) to 24 hours (h) postinjury. All animals were evaluated at the LM and EM levels. Those animals receiving intrathecal HRP showed immediate focal alterations in the axolemma's permeability to the normally excluded tracer. Over a 2 h period, these axons demonstrated NF compaction. Antibodies targeted to the rod domains revealed focal intra-axonal immunoreactivity in sites closely correlated with those showing altered axolemmal permeability. These same sites also demonstrated evidence of NF compaction and sidearm loss/perturbation. Collectively, these findings suggest that occurrence of altered axolemmal permeability and concomitant cytoskeletal change are features common to traumatic brain injury in various animal models and species. Further, these studies underscore the utility of antibodies targeting the rod domain for the early detection of traumatically induced reactive change.
最近我们报道，创伤性脑损伤会引起轴膜通透性的局部变化，同时伴有涉及神经丝（NF）压缩和侧臂丢失的局部细胞骨架变化，所有这些都促成了反应性轴突变化的发生。由于担心这些事件可能是损伤模型或物种特异性的，我们试图在另一种特征明确的动物模型和物种中研究这些现象。此外，为了更深入地了解NF压缩和侧臂改变的可能性，我们还使用了针对NF杆状结构域的特异性抗体，只有当NF侧臂受到干扰时，这些抗体才能很容易地被观察到。对大鼠进行撞击加速损伤。为了评估轴膜通透性改变的可能性，5只动物接受了鞘内注射辣根过氧化物酶（HRP），完整的轴膜通常会排除这种酶。为了评估NF侧臂改变的可能性，另外14只动物在受伤后5分钟（min）至24小时（h）进行处理，以观察针对NF杆状结构域的抗体。所有动物均在光镜和电镜水平进行评估。接受鞘内注射HRP的动物显示，轴膜对通常被排除的示踪剂的通透性立即发生局部改变。在2小时内，这些轴突显示出NF压缩。针对杆状结构域的抗体在与轴膜通透性改变部位密切相关的位点显示出局部轴突内免疫反应性。这些相同的位点也显示出NF压缩和侧臂丢失/扰动的证据。总的来说，这些发现表明，轴膜通透性改变和伴随的细胞骨架变化是各种动物模型和物种创伤性脑损伤的共同特征。此外，这些研究强调了针对杆状结构域的抗体在早期检测创伤性诱导反应性变化方面的实用性。
