Ke Ding1, Handong Wang2, Yong Wu1, Li Zhang1, Jianguo Xu1, Tao Li1, Yu Ding1, Lin Zhu1, Jin He1. 1. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. 2. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: njhdwang@hotmail.com.
Abstract
BACKGROUND: Rapamycin has proven to be a neuroprotective agent in traumatic brain injury (TBI). However, there is a lack of data regarding the effect of rapamycin on apoptotic neuronal death after TBI. Thus, the present study was designed to detect the modulatory role of rapamycin on apoptosis and explore the potential involvement of the mammalian target of rapamycin (mTOR)-p53-Bax axis after TBI. MATERIAL AND METHODS: Neurologic severity score tests were performed to measure behavioral outcomes. The effect of rapamycin treatment on neuronal death was analyzed using immunofluorescence analysis of NeuN. Terminal deoxynucleotidyl transferase-mediated dUTP nick 3'-end labeling was performed to detect apoptotic cells. The expression of Bax and phosphorylated protein of p53 was detected using Western blotting analyses and immunofluorescence staining. Phosphorylated protein of the mTOR in the ipsilateral cortex was detected using Western blotting analyses. RESULTS: Rapamycin administration after TBI was associated with an increased number of neurons, decreased apoptosis index, and improved neurobehavioral function, which was potentially mediated by inactivation of the mTOR-p53-Bax axis. CONCLUSIONS: Rapamycin can protect neurons from apoptotic neuronal death after TBI. This study presents a new insight into the antiapoptosis mechanisms, which are responsible for the neuroprotection of rapamycin, with the potential involvement of the mTOR-p53-Bax axis.
BACKGROUND:Rapamycin has proven to be a neuroprotective agent in traumatic brain injury (TBI). However, there is a lack of data regarding the effect of rapamycin on apoptotic neuronal death after TBI. Thus, the present study was designed to detect the modulatory role of rapamycin on apoptosis and explore the potential involvement of the mammalian target of rapamycin (mTOR)-p53-Bax axis after TBI. MATERIAL AND METHODS: Neurologic severity score tests were performed to measure behavioral outcomes. The effect of rapamycin treatment on neuronal death was analyzed using immunofluorescence analysis of NeuN. Terminal deoxynucleotidyl transferase-mediated dUTP nick 3'-end labeling was performed to detect apoptotic cells. The expression of Bax and phosphorylated protein of p53 was detected using Western blotting analyses and immunofluorescence staining. Phosphorylated protein of the mTOR in the ipsilateral cortex was detected using Western blotting analyses. RESULTS:Rapamycin administration after TBI was associated with an increased number of neurons, decreased apoptosis index, and improved neurobehavioral function, which was potentially mediated by inactivation of the mTOR-p53-Bax axis. CONCLUSIONS:Rapamycin can protect neurons from apoptotic neuronal death after TBI. This study presents a new insight into the antiapoptosis mechanisms, which are responsible for the neuroprotection of rapamycin, with the potential involvement of the mTOR-p53-Bax axis.
Authors: Erica L Littlejohn; Anthony J DeSana; Hannah C Williams; Rudy T Chapman; Binoy Joseph; Jelena A Juras; Kathryn E Saatman Journal: Front Cell Dev Biol Date: 2021-05-20