Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: autophagy and the PI3K/AKT pathways as a potential mechanism

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• 作者：Yongyue Gao ; MD ; Jie Li ; MD ; PhD ; ^{njLijiepro@126.com" class="auth_mail" title="E-mail the corresponding author} ; Lingyun Wu ; MD ; PhD ; Chenhui Zhou ; MD ; PhD ; Qiang Wang ; MD ; PhD ; Xiang Li ; MD ; Mengliang Zhou ; MD ; PhD ; Handong Wang ; MD ; PhD ; ^{njhdwang@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tetrahydrocurcumin ; Traumatic brain injury ; Apoptosis ; Autophagy ; PI3K/AKT signaling pathway
• 刊名：Journal of Surgical Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：206
• 期：1
• 页码：67-76
• 全文大小：1804 K

文摘

Tetrahydrocurcumin provides neuroprotection in multiple neurologic disorders by modulating oxidative stress, inflammatory responses, and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of tetrahydrocurcumin exists. In this study, we hypothesized that administration of tetrahydrocurcumin provides neuroprotection in a rat model of TBI.

Material and methods

Behavioral studies were performed by recording and analyzing beam-walking scores. The role of tetrahydrocurcumin on neurons death was assessed via Nissl staining. We then performed Western blot analyses, terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling assays and immunofluorescence staining to evaluate autophagy and apoptosis. Phospho-protein kinase B (p-AKT) was also assessed via Western blotting.

Results

Our data indicated that administration of tetrahydrocurcumin alleviated brain edema, attenuated TBI-induced neuron cell death, decreased the degree of apoptosis and improved neurobehavioral function, which were accompanied by enhanced autophagy and phospho-AKT after TBI. Moreover, the autophagy inhibitor 3-methyladenine and the PI3K kinase inhibitor LY294002 partially reversed the neuroprotection of tetrahydrocurcumin after TBI.

Conclusions

This study indicates that tetrahydrocurcumin protects neurons from TBI-induced apoptotic neuronal death, which may be through modulation autophagy and PI3K/AKT pathways. Thus, tetrahydrocurcumin may be an attractive therapeutic agent for TBI.