Yijie Duan, Weisheng Huang, Ji Zhang, Jiao Mu, Yiwu Zhou, Hongmei Dong
Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Hankou, Wuhan, People's Republic of China.
Int J Legal Med. 2023 May;137(3):843-849. doi: 10.1007/s00414-022-02938-3. Epub 2022 Dec 23.
Traumatic axonal injury (TAI) accounts for a large proportion of the mortality of traumatic brain injury (TBI). The diagnosis of TAI is currently of limited use for medicolegal purposes. It is known that axons in TAI are diffusely damaged by secondary processes other than direct head injury. However, the physiopathological mechanism of TAI is still elusive. The present study used RGD peptide, an antagonist of the mechanotransduction protein integrin, to explore the role of integrin-transmitted mechanical signalling in the pathogenesis of rat TAI. The rats were subjected to a linearly accelerating load, and changes in beta-amyloid precursor protein (β-APP) expression, skeleton ultrastructure, skeleton protein neurofilament light (NF-L), and α-tubulin in the brainstem were observed, indicating that RGD could relieve the severity of axonal injury in TAI rats. In addition, the expression of β-integrin was stronger and centralized in the brainstem of the deceased died from TAI compared to other nonviolent causes. This study examined the pathophysiology and biomechanics of TAI and assessed the role of integrin in the injury of microtubules and neurofilaments in TAI. Thus, we propose that integrin-mediated cytoskeletal injury plays an important role in TAI and that integrin has the potential as a biomarker for TAI.
创伤性轴索损伤(TAI)在创伤性脑损伤(TBI)的死亡病例中占很大比例。目前,TAI的诊断在法医学上的应用有限。已知TAI中的轴突会受到除直接头部损伤之外的继发性过程的弥漫性损伤。然而,TAI的生理病理机制仍然不清楚。本研究使用机械转导蛋白整合素的拮抗剂RGD肽,来探究整合素介导的机械信号在大鼠TAI发病机制中的作用。对大鼠施加线性加速负荷,并观察脑干中β-淀粉样前体蛋白(β-APP)表达、骨架超微结构、骨架蛋白神经丝轻链(NF-L)和α-微管蛋白的变化,表明RGD可以减轻TAI大鼠轴突损伤的严重程度。此外,与其他非暴力原因死亡者相比,死于TAI者脑干中β-整合素的表达更强且更集中。本研究探讨了TAI的病理生理学和生物力学,并评估了整合素在TAI中微管和神经丝损伤中的作用。因此,我们提出整合素介导的细胞骨架损伤在TAI中起重要作用,并且整合素具有作为TAI生物标志物的潜力。