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 in vivo and in vitro 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 in vitro TBI studies conducted from 2008–2018 to better understand the TBI in vitro model available in the literature. Specifically, our focus was to perform a detailed analysis of the in vitro 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 in vitro 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 in vivo 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.

中文翻译：

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创伤性脑损伤的体外模型：系统评价


创伤性脑损伤（TBI）是一项重大的公共卫生挑战，也是全球第三大死亡原因。它也是全世界儿童和年轻人长期残疾的主要原因。尽管大量研究主要使用体内和体外啮齿动物脑损伤模型，但目前还没有药物可以减少脑损伤或促进脑修复，这主要是由于我们对 TBI 的机制和病理生理学缺乏了解。本综述的目的是检查 2008 年至 2018 年进行的体外TBI 研究，以更好地了解文献中可用的 TBI体外模型。具体来说，我们的重点是对所使用的体外实验方案及其随后的生物学发现进行详细分析。我们的综述表明，单轴拉伸是最常用的载荷应用方式，占所综述研究的三分之二以上。不同研究的负荷速率和强度差异很大，但通常可分为轻度、中度和重度损伤。本文回顾的体外研究检查了 TBI 病理生理学的关键过程，例如导致离子失调、炎症以及随后对微管和轴突的损伤以及细胞死亡的膜破坏。总体而言，本综述中的研究有助于我们更好地理解 TBI 作为一种疾病过程。 然而，我们的审查还揭示了需要做更多工作的领域，例如：1）负载应用方法的多样化，包括模拟体内头部冲击的复杂负载； 2）在实验装置中更广泛地使用人类脑细胞，特别是与患者匹配的人类细胞； 3）需要构建更高通量的系统，以便能够发现 TBI 的有效治疗靶点。