Traumatic brain injury (TBI) is one of the most important causes of death and disability in adults and thus an important public health problem. Following TBI, secondary pathophysiological processes develop over time and condition the development of different neurodegenerative entities. Previous studies suggest that neurobehavioral changes occurring after a single TBI are the basis for the development of Alzheimer's disease, while repetitive TBI is considered to be a contributing factor for chronic traumatic encephalopathy development. However, pathophysiological processes that determine the evolvement of a particular chronic entity are still unclear. Human post-mortem studies have found combinations of amyloid, tau, Lewi bodies, and TAR DNA-binding protein 43 (TDP-43) pathologies after both single and repetitive TBI. This review focuses on the pathological changes of TDP-43 after single and repetitive brain traumas. Numerous studies have shown that TDP-43 proteinopathy noticeably occurs after repetitive head trauma. A relatively small number of available preclinical research on single brain injury are not in complete agreement with the results from the human samples, which makes it difficult to draw specific conclusions. Also, as TBI is considered a heterogeneous type of injury, different experimental trauma models and injury intensities may cause differences in the cascade of secondary injury, which should be considered in future studies. Experimental and post-mortem studies of TDP-43 pathobiology should be carried out, preferably in the same laboratories, to determine its involvement in the development of neurodegenerative conditions after one and repetitive TBI, especially in the context of the development of new therapeutic options.

中文翻译：

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单次与重复性创伤性脑损伤：关于慢性结果、神经病理学和 TDP-43 蛋白病作用的最新知识。

创伤性脑损伤（TBI）是成人死亡和残疾的最重要原因之一，因此是一个重要的公共卫生问题。TBI 后，继发性病理生理过程会随着时间的推移而发展，并影响不同神经退行性实体的发展。先前的研究表明，单次TBI后发生的神经行为变化是阿尔茨海默病发展的基础，而重复TBI被认为是慢性创伤性脑病发展的一个促成因素。然而，决定特定慢性实体进化的病理生理过程仍不清楚。人类尸检研究发现，单次和重复性 TBI 后都会出现淀粉样蛋白、tau 蛋白、路易斯小体和 TAR DNA 结合蛋白 43 (TDP-43) 病理的组合。本文重点讨论单次和重复性脑外伤后 TDP-43 的病理变化。大量研究表明，重复性头部创伤后会明显发生 TDP-43 蛋白病。现有的针对单一脑损伤的临床前研究相对较少，与人体样本的结果并不完全一致，这使得很难得出具体的结论。此外，由于TBI被认为是一种异质性损伤，不同的实验创伤模型和损伤​​强度可能会导致继发性损伤级联的差异，这一点应在未来的研究中考虑。应最好在同一实验室对 TDP-43 病理学进行实验和尸检研究，以确定其在一次和重复 TBI 后神经退行性疾病发展中的作用，特别是在开发新的治疗方案的背景下。