Ubiquitin-specific protease 11 (USP11) is a ubiquitin-specific protease involved in the regulation of protein ubiquitination. However, its role in traumatic brain injury (TBI) remains unclear. This experiment suggests that USP11 is possibly involved in regulating neuronal apoptosis in TBI. Therefore, we use precision impactor device to established a TBI rat model and assayed the role of USP11 by overexpressing and inhibiting USP11. We found that Usp11 expression increased after TBI. In addition, we hypothesized that pyruvate kinase M2 (PKM2) is a potential USP11 target and experimentally confirmed that upregulation of Usp11 increased Pkm2 expression. Furthermore, elevated USP11 levels exacerbate blood–brain barrier damage, brain edema, and neurobehavioral impairment and cause apoptosis induction through Pkm2 upregulation. Moreover, we hypothesize that PKM2-induced neuronal apoptosis is mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Our findings were confirmed by changes in Pi3k and Akt expression with Usp11 upregulation and downregulation and PKM2 inhibition. In conclusion, our findings show that USP11 exacerbates injury in TBI through PKM2 and causes neurological impairment and neuronal apoptosis through the PI3K/AKT signaling pathway.

泛素特异性蛋白酶 11 (USP11) 是一种泛素特异性蛋白酶，参与蛋白质泛素化的调节。然而，其在创伤性脑损伤 (TBI) 中的作用仍不清楚。该实验表明 USP11 可能参与调节 TBI 中的神经元凋亡。因此，我们采用精密撞击器建立TBI大鼠模型，通过过表达和抑制USP11来检测USP11的作用。我们发现TBI 后Usp11表达增加。此外，我们假设丙酮酸激酶 M2 (PKM2) 是潜在的 USP11 靶标，并通过实验证实Usp11的上调增加了Pkm2表达。此外，升高的 USP11 水平会加剧血脑屏障损伤、脑水肿和神经行为障碍，并通过Pkm2上调引起细胞凋亡。此外，我们假设 PKM2 诱导的神经细胞凋亡是由磷酸肌醇 3-激酶 (PI3K)/蛋白激酶 B (AKT) 信号通路介导的。我们的发现通过Pi3k和Akt表达的变化以及Usp11上调和下调以及 PKM2 抑制得到证实。总之，我们的研究结果表明，USP11 通过 PKM2 加剧了 TBI 损伤，并通过 PI3K/AKT 信号通路引起神经损伤和神经元凋亡。