Siedler Declan G, Chuah Meng Inn, Kirkcaldie Matthew T K, Vickers James C, King Anna E
Wicking Dementia Research and Education Centre, Medical Sciences Precinct Hobart, TAS, Australia ; School of Medicine, University of Tasmania Hobart, TAS, Australia.
Front Cell Neurosci. 2014 Dec 17;8:429. doi: 10.3389/fncel.2014.00429. eCollection 2014.
Traumatic brain injury (TBI) from penetrating or closed forces to the cranium can result in a range of forms of neural damage, which culminate in mortality or impart mild to significant neurological disability. In this regard, diffuse axonal injury (DAI) is a major neuronal pathophenotype of TBI and is associated with a complex set of cytoskeletal changes. The neurofilament triplet proteins are key structural cytoskeletal elements, which may also be important contributors to the tensile strength of axons. This has significant implications with respect to how axons may respond to TBI. It is not known, however, whether neurofilament compaction and the cytoskeletal changes that evolve following axonal injury represent a component of a protective mechanism following damage, or whether they serve to augment degeneration and progression to secondary axotomy. Here we review the structure and role of neurofilament proteins in normal neuronal function. We also discuss the processes that characterize DAI and the resultant alterations in neurofilaments, highlighting potential clues to a possible protective or degenerative influence of specific neurofilament alterations within injured neurons. The potential utility of neurofilament assays as biomarkers for axonal injury is also discussed. Insights into the complex alterations in neurofilaments will contribute to future efforts in developing therapeutic strategies to prevent, ameliorate or reverse neuronal degeneration in the central nervous system (CNS) following traumatic injury.
穿透性或闭合性颅脑外力导致的创伤性脑损伤（TBI）可引发一系列神经损伤形式，最终导致死亡或造成轻度至重度神经功能障碍。在这方面，弥漫性轴索损伤（DAI）是TBI的主要神经元病理表型，与一系列复杂的细胞骨架变化相关。神经丝三联体蛋白是关键的细胞骨架结构成分，对轴突的抗张强度可能也有重要作用。这对于轴突如何应对TBI具有重要意义。然而，尚不清楚轴突损伤后神经丝压缩和细胞骨架变化是损伤后保护机制的一部分，还是会加剧退变并发展为继发性轴突切断。在此，我们综述神经丝蛋白在正常神经元功能中的结构和作用。我们还讨论了DAI的特征过程以及神经丝的相应改变，强调了损伤神经元内特定神经丝改变可能具有的保护或退变影响的潜在线索。还讨论了神经丝检测作为轴突损伤生物标志物的潜在用途。对神经丝复杂变化的深入了解将有助于未来开发治疗策略，以预防、改善或逆转创伤性损伤后中枢神经系统（CNS）中的神经元退变。
