, Volume 41, Issue 4, pp 1182–1193 | Cite as

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

  • Wei Zhu
  • Yuexia Ding
  • Wei Kong
  • Tuo Li
  • Hongguang Chen


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.


traumatic brain injury Nrf2/ARE pathway docosahexaenoic acid (DHA) immunofluorescence 

List of Abbreviations


traumatic brain injury


glutathione peroxidase


superoxide dismutase


quinone oxidoreductase


heme oxygenase 1


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


nuclear factor erythroid 2-related factor 2


Kelch-like ECH-associated protein 1


docosahexaenoic acid




neurological severity score


wet weight


dry weight


electrophoresis mobility shift assay


transferase-mediated dUTP nick 3′-end labeling


Compliance with Ethical Standards

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

Conflicts of Interest

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantaiChina
  2. 2.Department of PharmacyThe Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantaiChina

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