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Fasudil attenuates glial cell-mediated neuroinflammation via ERK1/2 and AKT signaling pathways after optic nerve crush

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Abstract

To investigate the functional role of fasudil in optic nerve crush (ONC), and further explore its possible molecular mechanism. After ONC injury, the rats were injected intraperitoneally either with fasudil or normal saline once a day until euthanized. RGCs survival was assessed by retrograde labeling with FluoroGold. Retinal glial cells activation and population changes (GFAP, iba-1) were measured by immunofluorescence. The expressions of cleaved caspase 3 and 9, p-ERK1/2 and p-AKT were detected by western blot. The levels of the pro-inflammatory cytokines were determined using real-time polymerase chain reaction. Fasudil treatment inhibited RGCs apoptosis and reduced RGCs loss demonstrated by the decreased apoptosis-associated proteins expression and the increased fluorogold labeling of RGCs after ONC, respectively. In addition, the ONC + fasudil group compared had a significantly lower expression of GFAP and iba1 compared with the ONC group. The levels of pro-inflammatory cytokines were significantly reduced in the ONC + fasudil group than in the ONC group. Furthermore, the phosphorylation levels of ERK1/2 and AKT (p-ERK1/2 and p-AKT) were obviously elevated by the fasudil treatment. Our study demonstrated that fasudil attenuated glial cell-mediated neuroinflammation by up-regulating the ERK1/2 and AKT signaling pathways in rats ONC models. We conclude that fasudil may be a novel treatment for traumatic optic neuropathy.

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Acknowledgements

Chinese government provided financial support in the form of the National Natural Science Foundation of China (Grant Nos. 81560166, 81460087, 81660168, 81660161, 8176040227 and 81760172) and the Natural Science Foundation of Guangxi Zhuang Autonomous Region (Grant Nos. 2018GXNSFAA281128 and 2018GXNSFBA281066).

Funding

This study was supported by the National Natural Science Foundation of China (No. 81660161, 81560166, 81460087, 81660168, 8176040227 and 81760172), and the Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2018GXNSFAA281128 and No. 2018GXNSFBA281066) and Guangxi clinical ophthalmic research center (No. AD19245193).

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Author notes

  1. Wei Huang, Qianqian Lan and Li Jiang have contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, China

    Wei Huang, Qianqian Lan, Li Jiang, Fen Tang, Chaolan Shen, Hui Huang, Haibin Zhong, Jian Lv, Siming Zeng, Min Li, Qi Chen, Fan Xu & Ling Cui

  2. Guangxi Medical University, Nanning, 530021, China

    Wei Huang

  3. Guangzhou Medical University, Guangzhou, 511436, China

    Wenya Yan

  4. Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, China

    Zhongxiang Mo, Bing Hu, Ning Liang & Mingyuan Zhang

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  1. Wei Huang
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  2. Qianqian Lan
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Contributions

QL, LJ and FX conceived and designed the experiments. ZM, BH, NL and MZ performed the establishment of model and the intraperitoneal injection. The retrograde labeling of RGCs with FluoroGold was performed by WH, HH and JL. WH, LJ and WY performed the western blot analysis and immunofluorescence staining experiments. FT, CS and JL performed the qPCR. WH, QL, LJ, FT analyzed and interpreted the data. WH, QL, LJ, and LC edited the paper. HZ, SZ, ML, LC and FX read and approved the final manuscript.

Corresponding authors

Correspondence to Fan Xu or Ling Cui.

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Huang, W., Lan, Q., Jiang, L. et al. Fasudil attenuates glial cell-mediated neuroinflammation via ERK1/2 and AKT signaling pathways after optic nerve crush. Mol Biol Rep 47, 8963–8973 (2020). https://doi.org/10.1007/s11033-020-05953-y

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