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Enriched Endogenous Omega-3 Fatty Acids in Mice Ameliorate Parenchymal Cell Death After Traumatic Brain Injury

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Abstract

Currently no effective therapies are available for the treatment of traumatic brain injury (TBI). Early intervention that specifically provides neuroprotection is of most importance which profoundly influences the outcome of TBI. In the present study, we adopted a closed-skull mild TBI model to investigate potential roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in protecting against TBI. Using two-photon laser scanning microscopy (2PLSM), parenchymal cell death and reactive oxidative species (ROS) expression were directly observed and recorded after TBI through a thinned skull bone window. Fat-1 mice with high endogenous ω-3 PUFAs significantly inhibited ROS expression and attenuated parenchymal cell death after compression injury during the early injury phase. Elevated generation of glutathione (GSH) and neuroprotectin D1 (NPD1) in the parenchyma of fat-1 mice could be the contributor to the beneficial role of ω-3 PUFAs in TBI. The results of the study suggest that ω-3 PUFAs is an effective neuroprotectant as an early pharmacological intervention for TBI and the information derived from this study may help guide dietary advice for those who are susceptible to repetitive mild TBI.

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Acknowledgments

This study was supported by the Macao Science and Technology Development Fund (063/2015/A1), multi-year research grant, University of Macau, MYRG122 (Y1-L3)-ICMS12-SHX and MYRG110 (Y1-L2)-ICMS13-SHX, the National Natural Scientific Foundation of China (31270992 and 30800215), Zhu Jiang Science and Technology New Star of Guangzhou City (2013 J2200019), Guangdong Province Science and Technology Plan (2013B021800275), and the Fundamental Research Funds for the Central Universities in Sun Yat-Sen University (13ykpy24).

Author Contributions

HR and HS designed the study; RH, ZY, CL, HZ, PL, CH, JK, JW, and HS performed and analyzed the results; and all authors wrote the draft together and approved the final version.

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    Authors and Affiliations

    1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

      Huixia Ren, Chuanming Luo, Peng Li, Jian-Bo Wan, Chengwei He & Huanxing Su

    2. Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

      Zhen Yang

    3. Center for Reproductive Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

      Haitao Zeng

    4. Laboratory for Lipid Medicine and Technology, the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

      Jing X Kang

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    1. Huixia Ren
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    Huixia Ren and Zhen Yang contributed equally to this work.

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    Ren, H., Yang, Z., Luo, C. et al. Enriched Endogenous Omega-3 Fatty Acids in Mice Ameliorate Parenchymal Cell Death After Traumatic Brain Injury. Mol Neurobiol 54, 3317–3326 (2017). https://doi.org/10.1007/s12035-016-9931-1

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