Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells after IL-12 administration

被引:48
作者
Yaguchi, Masae [1 ]
Ohta, Shigeki [1 ]
Toyama, Yoshiaki [2 ]
Kawakami, Yutaka [3 ]
Toda, Masahiro [1 ,4 ]
机构
[1] Keio Univ, Sch Med, Neuroimmunol Res Grp, Shinjuku Ku, Keio, Japan
[2] Keio Univ, Sch Med, Dept Orthopaed Surg, Keio, Japan
[3] Keio Univ, Sch Med, Inst Adv Med Res, Div Cellular Signaling, Tokyo, Japan
[4] Keio Univ, Sch Med, Dept Neurosurg, Tokyo 160, Japan
关键词
IL-12; microglia; spinal cord injury; dendritic cells; BDNF; neurogenesis;
D O I
10.1002/jnr.21658
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have previously reported that the transplantation of dendritic cells (DCs) brings about functional recovery after spinal cord injury in mice through the activation of endogenous microglia/macrophages and neural stem/progenitor cells. In this study, the effect of interleukin-12 (IL-12), which is secreted from DCs, was evaluated for the treatment of spinal cord injury in mice. Administration of IL-12 into the injured site significantly increased the number of activated microglia/macrophages and DCs as well as the expression of brain-derived neurotrophic factor surrounding the lesion site. Immunohistochemical analyses showed that de novo neurogenesis and remyelination were induced by IL-12 treatment. Furthermore, an open field test using Basso-Beattie-Brenham scoring revealed a significant improvement of locomotor function in mice treated with IL-12. These results suggest that IL-12 administration into the injured spinal cord results in a functional recovery through the activation of microglia/macrophages and DCs. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:1972 / 1980
页数:9
相关论文
共 52 条
  • [21] Interleukin-12 promotes neurite outgrowth in mouse sympathetic superior cervical ganglion neurons
    Lin, HY
    Hikawa, N
    Takenaka, T
    Ishikawa, Y
    [J]. NEUROSCIENCE LETTERS, 2000, 278 (03) : 129 - 132
  • [22] CNS dendritic cells: Critical participants in CNS inflammation?
    McMahon, Eileen J.
    Bailey, Samantha L.
    Miller, Stephen D.
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2006, 49 (02) : 195 - 203
  • [23] Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery
    Mikami, Y
    Okano, H
    Sakaguchi, M
    Nakamura, M
    Shimazaki, T
    Okano, HJ
    Kawakami, Y
    Toyama, Y
    Toda, M
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2004, 76 (04) : 453 - 465
  • [24] Miwa T, 1997, J NEUROSCI RES, V50, P1023
  • [25] Divergent pro- and Antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation
    Murphy, CA
    Langrish, CL
    Chen, Y
    Blumenschein, C
    McClanahan, T
    Kastelein, RA
    Sedgwick, JD
    Cua, DJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) : 1951 - 1957
  • [26] Neurotrophin secretion from cultured microglia
    Nakajima, K
    Honda, S
    Tohyama, Y
    Imai, Y
    Kohsaka, S
    Kurihara, T
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 65 (04) : 322 - 331
  • [27] Brain-derived neurotrophic factor reduces necrotic zone and supports neuronal survival after spinal cord hemisection in adult rats
    Novikova, L
    Novikov, L
    Kellerth, JO
    [J]. NEUROSCIENCE LETTERS, 1996, 220 (03) : 203 - 206
  • [28] Popovich PG, 1997, J COMP NEUROL, V377, P443, DOI 10.1002/(SICI)1096-9861(19970120)377:3<443::AID-CNE10>3.0.CO
  • [29] 2-S
  • [30] Portielje JEA, 1999, CLIN CANCER RES, V5, P3983