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Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling

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Abstract

In this study, we explored the neuroprotective effects of docosahexaenoic acid (DHA) in traumatic brain injury (TBI) models. In this study, we first confirmed that DHA was neuroprotective against TBI via the NSS test and Morris water maze experiment. Western blot was conducted to identify the expression of Bax, caspase-3, and Bcl-2. And the cell apoptosis of the TBI models was validated by TUNEL staining. Relationships between nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway-related genes and DHA were explored by RT-PCR and Western blot. Rats of the DHA group performed remarkably better than those of the TBI group in both NSS test and water maze experiment. DHA conspicuously promoted the expression of Bcl-2 and diminished that of cleaved caspase-3 and Bax, indicating the anti-apoptotic role of DHA. Superoxide dismutase (SOD) activity and cortical malondialdehyde content, glutathione peroxidase (GPx) activity were renovated in rats receiving DHA treatment, implying that the neuroprotective influence of DHA was derived from lightening the oxidative stress caused by TBI. Moreover, immunofluorescence and Western blot experiments revealed that DHA facilitated the translocation of Nrf2 to the nucleus. DHA administration also notably increased the expression of the downstream factors NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1(HO-1). DHA exerted neuroprotective influence on the TBI models, potentially through activating the Nrf2- ARE pathway.

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Abbreviations

TBI:

traumatic brain injury

GPx:

glutathione peroxidase

SOD:

superoxide dismutase

NQO-1:

quinone oxidoreductase

HO-1:

heme oxygenase 1

Nrf2-ARE:

nuclear factor erythroid 2-related factor 2-antioxidant response element

Nrf2:

nuclear factor erythroid 2-related factor 2

Keap1:

Kelch-like ECH-associated protein 1

DHA:

docosahexaenoic acid

LPS:

lipopolysaccharide

NSS:

neurological severity score

WW:

wet weight

DW:

dry weight

EMSA:

electrophoresis mobility shift assay

TUNEL:

transferase-mediated dUTP nick 3′-end labeling

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Author notes

  1. Wei Zhu and Yuexia Ding contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 East Yuhuangding Road, Zhifu District, Yantai, 264000, Shandong, China

    Wei Zhu, Wei Kong, Tuo Li & Hongguang Chen

  2. Department of Pharmacy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, China

    Yuexia Ding

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  1. Wei Zhu
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Correspondence to Wei Zhu.

Ethics declarations

This animal experiment had been approved and followed the protocols of the Ethics Committee of the Affiliated Yantai Yuhuangding Hospital of Qingdao University.

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The authors declare that they have no conflict of interests.

Research Involving Human Participants and/or Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

This animal experiment had been approved and followed the protocols of the Ethics Committee of the Affiliated Yantai Yuhuangding Hospital of Qingdao University.

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Zhu, W., Ding, Y., Kong, W. et al. Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling. Inflammation 41, 1182–1193 (2018). https://doi.org/10.1007/s10753-018-0765-z

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