Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, in part resulting from secondary apoptosis of neurons in peri-contusion areas. Serpina3k, a serine protease inhibitor, has been shown to inhibit apoptosis in injury models. In this study, we investigated the anti-apoptotic function of serpina3k in vivo using a mouse model of TBI, as well as the underlying neuroprotective mechanism in vitro using the SH-SY5Y human neuroblastoma cell line. TBI was induced in adult male C57BL/6 mice using controlled cortical impact. Serpina3k protein was intravenously administered at a concentration of 0.5 mg/kg twice daily for up to 14 days. SH-SY5Y cells were subjected to biaxial stretch injury and then treated with different concentrations of serpina3k. We found that endogenous serpina3k protein levels were elevated in peri-contusion areas of the mouse brain following TBI. Serpina3k-treated mice had fewer apoptotic neurons, lower levels of oxidative stress, and showed greater recovery of neurological deficits relative to vehicle-treated mice. Meanwhile, in the SH-SY5Y cell injury model, serpina3k at an optimal concentration (150 nM) inhibited the generation of intracellular reactive oxygen species, abrogated changes of the mitochondrial membrane potential, and reduced the phospho-extracellular regulated protein kinases (p-ERK)/ERK, phospho-P38 (p-P38)/P38, B cell lymphoma (Bcl)-2-associated X protein/Bcl-2, and cleaved caspase-3/caspase-3 ratios, thereby reducing the apoptosis rate. These results demonstrate that serpina3k exerts a neuroprotective function following TBI and thus has therapeutic potential.

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antiapoptotic stress tbi caspase3caspase3 stretch mitochondrial membrane phosphoextracellular regulated protein kinases serpina3k protein apoptosis intracellular reactive oxygen cell lymphoma

Yao Jing,Dianxu Yang,Yimu Fu,Wei Wang,Guoyuan Yang,Fang Yuan,Hao Chen,Jun Ding,Shiwen Chen,Hengli Tian,.Neuroprotective Effects of Serpina3k in Traumatic Brain Injury. 10 (),.

Yao Jing,Dianxu Yang,Yimu Fu,Wei Wang,Guoyuan Yang,Fang Yuan,Hao Chen,Jun Ding,Shiwen Chen,Hengli Tian,"Neuroprotective Effects of Serpina3k in Traumatic Brain Injury" 10

Yao Jing,Dianxu Yang,Yimu Fu,Wei Wang,Guoyuan Yang,Fang Yuan,Hao Chen,Jun Ding,Shiwen Chen,Hengli Tian,"Neuroprotective Effects of Serpina3k in Traumatic Brain Injury"