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Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor

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Abstract

Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive gliosis after spinal cord injury (SCI), and blocking the PAF pathway would modify the glia scar formation and promote functional recovery. PAF microinjected into the normal wild-type spinal cord induced a dose-dependent activation of microglia and astrocytes. In the SCI mice, PAFR null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and PAFR null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in PAFR null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in PAFR null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth.

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Acknowledgments

This work was supported by pilot grants of NIH (P30 GM103507-04) and Department of Pediatrics, NSFC (81400998), NSFC (81360195), State Key Program of NSFC (81330042), Sino-Russian Joint Research Program of MSTC (2014DFR31210), Key Program of Tianjin STCC (13RCGFSY19000, 14ZCZDSY00044), and CSC scholarship. The authors would like to thank Dr. Theo Hagg for his critical comments on experimental design.

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The authors report no conflicts of interest.

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    Authors and Affiliations

    1. Department of Spine Surgery, First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, People’s Republic of China

      Yuanyi Wang

    2. Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA

      Yuanyi Wang, Zhongwen Gao, Shi-Qing Feng, Yulong Liu, Ying-Zheng Zhao & Jun Cai

    3. Norton Healthcare, Norton Neuroscience Institute, Louisville, KY, 40202, USA

      Yiping Zhang, Lisa B. E. Shields & Christopher B. Shields

    4. Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, 300052, China

      Shi-Qing Feng

    5. Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, China

      Zhongwen Gao, Yulong Liu & Qingsan Zhu

    6. Pharmacy School, Wenzhou Medical University, Wenzhou, 325035, China

      Ying-Zheng Zhao

    7. Comer Children’s Hospital, Department of Pediatrics, University of Chicago, Chicago, IL, 60637, USA

      David Gozal

    8. Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA

      Christopher B. Shields & Jun Cai

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    Correspondence to Qingsan Zhu or Jun Cai.

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    Yuanyi Wang, Zhongwen Gao and Yiping Zhang contributed equally to this work.

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    Wang, Y., Gao, Z., Zhang, Y. et al. Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor. Mol Neurobiol 53, 3448–3461 (2016). https://doi.org/10.1007/s12035-015-9263-6

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