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Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice

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Abstract

Macrophage migration inhibitory factor (MIF) is a multipotential protein that acts as a proinflammatory cytokine, a pituitary hormone, and a cell proliferation and migration factor. The objective of this study was to elucidate the role of MIF in spinal cord injury (SCI) using female MIF knockout (KO) mice. Mouse spinal cord compression injury was produced by application of a static load (T8 level, 20 g, 5 min). We analyzed the motor function of the hind limbs and performed histological examinations. Hind-limb function recovered significantly in the KO mice starting from three weeks after injury. Cresyl-violet staining revealed that the number of surviving neurons in the KO mice was significantly larger than that of WT mice six weeks after injury. Immunohistochemical analysis revealed that the number of NeuN/caspase-3-active, double-positive, apoptotic neurons in the KO mice was significantly smaller than that of the WT mice 24 and 72 h after SCI. These results were related to in-vitro studies showing increased resistance of cerebellar granular neurons from MIF-KO animals to glutamate neurotoxicity. These results suggest that MIF existence hinders neuronal survival after SCI. Suppression of MIF may attenuate detrimental secondary molecular responses of the injured spinal cord.

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Acknowledgments

We thank Dr Toshinori Nakayama of Department of Immunology, Graduate School of Medicine, Chiba University, for management of animal supply and useful discussions about this paper.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Yutaka Nishio, Masao Koda, Masayuki Hashimoto, Takahito Kamada, Shuhei Koshizuka, Katsunori Yoshinaga, Akihiko Okawa & Masashi Yamazaki

  2. Department of Sports Medicine and Joint Reconstruction Surgery, Graduate School of Medicine, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan

    Shin Onodera

  3. Department of Medical Bioinformatics, Hokkaido Information University, 59-2 Nishinopporo, Ebetsu, Hokkaido, 069-8585, Japan

    Jun Nishihira

Authors
  1. Yutaka Nishio
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  2. Masao Koda
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  3. Masayuki Hashimoto
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  4. Takahito Kamada
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  5. Shuhei Koshizuka
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  6. Katsunori Yoshinaga
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  7. Shin Onodera
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  8. Jun Nishihira
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  9. Akihiko Okawa
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  10. Masashi Yamazaki
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Corresponding author

Correspondence to Masayuki Hashimoto.

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Nishio, Y., Koda, M., Hashimoto, M. et al. Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice. Acta Neuropathol 117, 321–328 (2009). https://doi.org/10.1007/s00401-008-0476-x

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  • DOI: https://doi.org/10.1007/s00401-008-0476-x

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