Shenyang Medical College, No. 146, Huanghe North Street, Shenyang 110034, China.
Department of Tumor Radiotherapy, the General Hospital of Northern Theater Command, No. 83 Road, Shenhe District, Shenyang l10016, China.
Brain Res Bull. 2024 Aug;214:110987. doi: 10.1016/j.brainresbull.2024.110987. Epub 2024 Jun 1.
In modern war or daily life, blast-induced traumatic brain injury (bTBI) is a growing health concern. Our previous studies demonstrated that inflammation was one of the main features of bTBI, and CD28-activated T cells play a central role in inflammation. However, the mechanism of CD28 in bTBI remains to be elucidated. In this study, traumatic brain injury model induced by chest blast exposure in male mice was established, and the mechanism of CD28 in bTBI was studied by elisa, immunofluorescence staining, flow cytometry analysis and western blot. After exposure to chest shock wave, the inflammatory factors IL-4, IL-6 and HMGB1 in serum were increased, and CD3 T cells, CD4 and CD8 T cell subsets in the lung were activated. In addition, chest blast exposure resulted in impaired spatial learning and memory ability, disruption of the blood-brain barrier (BBB), and the expression of Tau, p-tau, S100β and choline acetyltransferase were increased. The results indicated that genetic knockdown of CD28 could inhibit inflammatory cell infiltration, as well as the activation of CD3 T cells, CD4 and CD8 T cell subsets in the lung, improve spatial learning and memory ability, and ameliorate BBB disruption and hippocampal neuron damage. Moreover, genetic knockdown of CD28 could reduce the expression of p-PI3K, p-AKT and NF-κB. In conclusion, chest blast exposure could lead to bTBI, and attenuate bTBI via the PI3K/AKT/NF-κB signaling pathway in male mice. This study provides new targets for the prevention and treatment of veterans with bTBI.
在现代战争或日常生活中，爆炸导致的创伤性脑损伤（bTBI）是一个日益严重的健康问题。我们之前的研究表明，炎症是 bTBI 的主要特征之一，而 CD28 激活的 T 细胞在炎症中发挥核心作用。然而，CD28 在 bTBI 中的作用机制仍有待阐明。在这项研究中，通过胸部爆炸暴露在雄性小鼠中建立创伤性脑损伤模型，并通过 ELISA、免疫荧光染色、流式细胞术分析和 Western blot 研究 CD28 在 bTBI 中的作用机制。胸部冲击波暴露后，血清中炎症因子 IL-4、IL-6 和 HMGB1 增加，肺中的 CD3 T 细胞、CD4 和 CD8 T 细胞亚群被激活。此外，胸部爆炸暴露导致空间学习和记忆能力受损，血脑屏障（BBB）破坏，Tau、p-tau、S100β 和胆碱乙酰转移酶的表达增加。结果表明，CD28 的基因敲低可以抑制炎症细胞浸润，以及肺中 CD3 T 细胞、CD4 和 CD8 T 细胞亚群的激活，改善空间学习和记忆能力，并改善 BBB 破坏和海马神经元损伤。此外，CD28 的基因敲低可以降低 p-PI3K、p-AKT 和 NF-κB 的表达。总之，胸部爆炸暴露可导致 bTBI，并通过雄性小鼠中的 PI3K/AKT/NF-κB 信号通路减轻 bTBI。这项研究为预防和治疗退伍军人的 bTBI 提供了新的靶点。
