Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
Center for Brain Research, The University of Auckland, Auckland, New Zealand.
J Neurotrauma. 2021 Sep 1;38(17):2336-2372. doi: 10.1089/neu.2020.7402. Epub 2021 Mar 12.
Traumatic brain injury (TBI) is a major public health challenge that is also the third leading cause of death worldwide. It is also the leading cause of long-term disability in children and young adults worldwide. Despite a large body of research using predominantly and rodent models of brain injury, there is no medication that can reduce brain damage or promote brain repair mainly due to our lack of understanding in the mechanisms and pathophysiology of the TBI. The aim of this review is to examine TBI studies conducted from 2008-2018 to better understand the TBI model available in the literature. Specifically, our focus was to perform a detailed analysis of the experimental protocols used and their subsequent biological findings. Our review showed that the uniaxial stretch is the most frequently used way of load application, accounting for more than two-thirds of the studies reviewed. The rate and magnitude of the loading were varied significantly from study to study but can generally be categorized into mild, moderate, and severe injuries. The studies reviewed here examined key processes in TBI pathophysiology such as membrane disruptions leading to ionic dysregulation, inflammation, and the subsequent damages to the microtubules and axons, as well as cell death. Overall, the studies examined in this review contributed to the betterment of our understanding of TBI as a disease process. Yet, our review also revealed the areas where more work needs to be done such as: 1) diversification of load application methods that will include complex loading that mimics head impacts; 2) more widespread use of human brain cells, especially patient-matched human cells in the experimental set-up; and 3) need for building a more high-throughput system to be able to discover effective therapeutic targets for TBI.
创伤性脑损伤（TBI）是一个主要的公共卫生挑战，也是全球范围内的第三大致死原因。它也是全球儿童和青年长期残疾的主要原因。尽管有大量使用主要是 和 啮齿动物脑损伤模型的研究，但由于我们对 TBI 的机制和病理生理学缺乏了解，没有药物可以减少脑损伤或促进脑修复。本综述的目的是检查 2008-2018 年期间进行的 TBI 研究，以更好地了解文献中可用的 TBI 模型。具体来说，我们的重点是对使用的实验方案进行详细分析及其随后的生物学发现。我们的综述表明，单轴拉伸是最常用的加载方式，占综述研究的三分之二以上。加载的速率和幅度在研究之间差异很大，但通常可以分为轻度、中度和重度损伤。这里回顾的 研究检查了 TBI 病理生理学中的关键过程，如导致离子失调、炎症和随后对微管和轴突的损伤的膜破裂，以及细胞死亡。总的来说，本综述中检查的研究有助于更好地了解 TBI 作为一种疾病过程。然而，我们的综述也揭示了需要进一步研究的领域，例如：1）多样化的加载方法，包括模仿 头部冲击的复杂加载；2）更广泛地使用人脑细胞，特别是在实验设置中使用患者匹配的人类细胞；3）需要建立一个更高通量的系统，以便能够发现 TBI 的有效治疗靶点。
