title: Tetrahydrocurcumin reduces oxidative stress-induced apoptosis via the mitochondrial apoptotic pathway by modulating autophagy in rats after traumatic brain injury.
abstract: Tetrahydrocurcumin (THC) has been identified as a multi-functional neuroprotective agent in numerous neurological disorders. Oxidative stress as a result of injury may induce neuronal apoptosis after traumatic brain injury (TBI). Treatment with THC may improve neurological function following TBI by attenuating oxidative stress and apoptosis and by enhancing autophagy. The purpose of this study was to investigate the mechanism of neuroprotection by THC against oxidative stress-induced neuronal apoptosis after TBI. We hypothesized that neuroprotection by THC may involve modulation of autophagy and the mitochondria apoptotic pathway. We used western blot analysis to evaluate the effect of THC on proteins involved in mitochondrial autophagy and apoptosis after TBI. The terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and immunofluorescence staining were used to confirm the role of THC in apoptosis and autophagy, respectively. THC-induced neuroprotection was assessed by neurological severity scoring (NSS) and by measuring the brain water content. We demonstrated that treatment with THC increased expression of autophagy-associated proteins LC3-II and Beclin-1 at 24 h post-TBI. Treatment with THC also reduced expression of malondialdehyde (MDA) and increased glutathione peroxidase (GPx) activity. Further, treatment with THC attenuated apoptosis by modulating mitochondrial apoptosis and reducing oxidative stress. Treatment with 3-methyladenine (3-MA) mitigated autophagy activation and reversed the inhibitory effect of THC on the translocation of Bax to the mitochondrial membrane. Moreover, treatment with THC improved neurological function and reduced the brain water content in rats after TBI. We concluded that the neuroprotective effects of THC are mediated by enhancing autophagy activation and by attenuation of oxidative stress and apoptosis after TBI, probably by modulating the mitochondrial apoptotic pathway. We suggest that THC may be an effective therapeutic agent to treat TBI.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Zong
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of General Surgery, Drum Tower Hospital, School of Medicine, Nanjing University Nanjing 210008, Jiangsu Province, China.
authors.forename: Shanting
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Zhongdu Hospital Bengbu 233015, Anhui Province, China.
authors.forename: Zihuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University Nanjing 210002, Jiangsu Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing 210002, Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
keywords: Traumatic brain injury; autophagy; mitochondrial apoptosis pathway; oxidative stress; tetrahydrocurcumin