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dl-3-n-Butylphthalide (NBP) Provides Neuroprotection in the Mice Models After Traumatic Brain Injury via Nrf2-ARE Signaling Pathway

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Abstract

The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou’s weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis. Furthermore, the level of malondialdehyde and the activity of superoxide dismutase (SOD) paired with glutathione peroxidase (GPx) were restored in the NBP treatment group. NBP promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus markedly, increased the expressions of Nrf2-ARE pathway-related downstream factors, including hemeoxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and prevented the decline of antioxidant enzyme activities, including SOD and GPx. NBP enhanced the translocation of Nrf2 to the nucleus from the cytoplasm,verified by a western blot, immunofluorescence. Additionally, it upregulated the expression of the Nrf2 downstream factors such as HO-1 and NQO1 were also confirmed via a western blot and real-time quantitative polymerase chain reaction. In conclusion, NBP administration may increase the activities of antioxidant enzymes and attenuate brain injury in a TBI model, potentially via the mediation of the Nrf2-ARE pathway.

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Abbreviations

NBP:

dl-3-n-Butylphthalide

Nrf2:

Nuclear factor erythroid 2-related factor 2

ARE:

Antioxidant response element

TBI:

Traumatic brain injury

TBI+V:

Traumatic brain injury+vehicle

TBI+NBP:

Traumatic brain injury+dl-3-n-Butylphthalide

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

GPx:

Glutathione peroxidase

HO-1:

Hemeoxygenase-1

NQO1:

NAD(P)H: quinone oxidoreductase 1

i.p:

Intraperitoneal injection

RT-qPCR:

Real-time quantitative polymerase chain reaction

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (No. 81371357) and National Natural Science Foundation of China (No. 81571162).

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Authors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People’s Republic of China

    Zhengwei Liu, Handong Wang, Hui Ding & Youqing Yang

  2. Department of Neurosurgery, Shenzhen Longgang Central Hospital, 6082 Longgangdadao Road, Shenzhen, 518116, Guangdong, People’s Republic of China

    Zhengwei Liu & Xiaofeng Shi

  3. Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People’s Republic of China

    Liwen Li, Mengliang Zhou, Xiang Li & Ke Ding

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  1. Zhengwei Liu
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Correspondence to Handong Wang.

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Liu, Z., Wang, H., Shi, X. et al. dl-3-n-Butylphthalide (NBP) Provides Neuroprotection in the Mice Models After Traumatic Brain Injury via Nrf2-ARE Signaling Pathway. Neurochem Res 42, 1375–1386 (2017). https://doi.org/10.1007/s11064-017-2186-z

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  • DOI: https://doi.org/10.1007/s11064-017-2186-z

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