Silencing CD28 attenuated chest blast exposure-induced traumatic brain injury through the PI3K/AKT/NF-κB signaling pathway in male mice.

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.