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Docosahexaenoic Acid Alleviates Oxidative Stress-Based Apoptosis Via Improving Mitochondrial Dynamics in Early Brain Injury After Subarachnoid Hemorrhage

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Abstract

Mitochondrial dysfunction is considered a crucial therapeutic target for early brain injury following subarachnoid hemorrhage (SAH). Emerging evidence indicates that docosahexaenoic acid (DHA), an essential omega-3 fatty acid, protects mitochondria in various chronic diseases. This study aimed to investigate the neuroprotective effects of DHA on mitochondrial dynamic dysfunction after EBI using in vivo and in vitro approaches. For in vivo experiments, the rat endovascular perforation SAH model was performed, whereby DHA was administered intravenously 1 h after induction of SAH. Primary cultured neurons treated with oxyhemoglobin (OxyHb) for 24 h were used to mimic SAH in vitro. Our results demonstrated that DHA improved neurological deficits and reduced brain edema in rats with SAH, and attenuated OxyHb-induced neuronal death in primary cultured cells. DHA reduced the amount of reactive oxygen species-positive cells and improved cell viability when compared to the SAH + vehicle group in vitro. DHA attenuated malondialdehyde levels and superoxide dismutase stress, increased Bcl2 and Bcl-xl, and decreased Bax and cleaved caspase-3 in vivo. Additionally, DHA ameliorated mitochondrial dysfunction, upregulated the mitochondrial fusion-related protein Optic Atrophy 1, and downregulated the mitochondrial fission-related protein Dynamin-Related-Protein 1 (Drp1) and Serine 616 phosphorylated Drp1 after SAH both in vitro and in vivo. Taken together, our current study demonstrates that DHA might prevent oxidative stress-based apoptosis after SAH. The characterization of the underlying molecular mechanisms may further improve mitochondrial dynamics-related signaling pathways.

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Acknowledgements

This study was funded by the Fundamental Research Funds for the Provincial Universities (2017LCZX30).

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Author notes

  1. Tongyu Zhang and Pei Wu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

    Tongyu Zhang, Pei Wu, Yuchen Li, Shancai Xu, Chunlei Wang, Ligang Wang, Guang Zhang, Jiaxing Dai, Shiyi Zhu, Yao Liu, Binbing Liu & Huaizhang Shi

  2. Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

    John H. Zhang & Cesar Reis

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  1. Tongyu Zhang
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Contributions

All authors listed contributed immensely to this study. TZ and PW performed the experiments, wrote the paper. YL, YL, and BL helped to perform the animal experiments. CW, LW, GZ, JD, SZ analyzed the data. HS, JHZ, and S X, as experts in neurology, provided technical supports and designed the research. Cesar Reis has proofread this manuscript.

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Correspondence to Huaizhang Shi.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Zhang, T., Wu, P., Zhang, J.H. et al. Docosahexaenoic Acid Alleviates Oxidative Stress-Based Apoptosis Via Improving Mitochondrial Dynamics in Early Brain Injury After Subarachnoid Hemorrhage. Cell Mol Neurobiol 38, 1413–1423 (2018). https://doi.org/10.1007/s10571-018-0608-3

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  • DOI: https://doi.org/10.1007/s10571-018-0608-3

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