Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia.
Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada.
Int J Mol Sci. 2021 Nov 11;22(22):12211. doi: 10.3390/ijms222212211.
Traumatic brain injury (TBI) is a disabling disorder and a major cause of death and disability in the world. Both single and repetitive traumas affect the brain acutely but can also lead to chronic neurodegenerative changes. Clinical studies have shown some dissimilarities in transactive response DNA binding protein 43 (TDP-43) expression patterns following single versus repetitive TBI. We explored the acute cortical post-traumatic changes of TDP-43 using the lateral fluid percussion injury (LFPI) model of single moderate TBI in adult male mice and investigated the association of TDP-43 with post-traumatic neuroinflammation and synaptic plasticity. In the ipsilateral cortices of animals following LFPI, we found changes in the cytoplasmic and nuclear levels of TDP-43 and the decreased expression of postsynaptic protein 95 within the first 3 d post-injury. Subacute pathological changes of TDP-43 in the hippocampi of animals following LFPI and in mice exposed to repetitive mild TBI (rmTBI) were studied. Changes in the hippocampal TDP-43 expression patterns at 14 d following different brain trauma procedures showed pathological alterations only after single moderate, but not following rmTBI. Hippocampal LFPI-induced TDP-43 pathology was not accompanied by the microglial reaction, contrary to the findings after rmTBI, suggesting that different types of brain trauma may cause diverse pathophysiological changes in the brain, specifically related to the TDP-43 protein as well as to the microglial reaction. Taken together, our findings may contribute to a better understanding of the pathophysiological events following brain trauma.
创伤性脑损伤 (TBI) 是一种使人丧失能力的疾病，也是世界上死亡和残疾的主要原因。单次和重复创伤都会对大脑造成急性影响，但也可能导致慢性神经退行性变化。临床研究表明，单次与重复 TBI 后，转导反应 DNA 结合蛋白 43（TDP-43）的表达模式存在一些差异。我们使用成年雄性小鼠的单次中度颅脑冲击伤（LFPI）模型研究了 TDP-43 在急性皮质创伤后的变化，并研究了 TDP-43 与创伤后神经炎症和突触可塑性的关系。在 LFPI 后动物的对侧皮质中，我们发现 TDP-43 的细胞质和核内水平发生变化，突触后蛋白 95 的表达在损伤后 3 天内下降。研究了 LFPI 后动物海马和重复轻度 TBI（rmTBI）暴露小鼠中海马 TDP-43 的亚急性病理变化。不同脑创伤程序后 14 天海马 TDP-43 表达模式的变化仅在单次中度损伤后显示出病理性改变，而在 rmTBI 后则没有。海马 LFPI 诱导的 TDP-43 病理学变化没有伴随着小胶质细胞反应，与 rmTBI 后的发现相反，这表明不同类型的脑创伤可能导致大脑中不同的病理生理变化，特别是与 TDP-43 蛋白以及小胶质细胞反应有关。总之，我们的发现可能有助于更好地理解脑创伤后的病理生理事件。
