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
  • [1] TNFα promotes proliferation of oligodendrocyte progenitors and remyelination
    Arnett, HA
    Mason, J
    Marino, M
    Suzuki, K
    Matsushima, GK
    Ting, JPY
    [J]. NATURE NEUROSCIENCE, 2001, 4 (11) : 1116 - 1122
  • [2] A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS
    BASSO, DM
    BEATTIE, MS
    BRESNAHAN, JC
    [J]. JOURNAL OF NEUROTRAUMA, 1995, 12 (01) : 1 - 21
  • [3] Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge
    Batchelor, PE
    Porritt, MJ
    Martinello, P
    Parish, CL
    Liberatore, GT
    Donnan, GA
    Howells, DW
    [J]. MOLECULAR AND CELLULAR NEUROSCIENCE, 2002, 21 (03) : 436 - 453
  • [4] Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages
    Bouhy, Delphine
    Malgrange, Brigitte
    Multon, Sylvie
    Poirrier, Anne-Lise
    Scholtes, Felix
    Schoenen, Jean
    Franzen, Rachelle
    [J]. FASEB JOURNAL, 2006, 20 (08) : 1239 - +
  • [5] Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury
    Brewer, KL
    Bethea, JR
    Yezierski, RP
    [J]. EXPERIMENTAL NEUROLOGY, 1999, 159 (02) : 484 - 493
  • [6] Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury
    Donnelly, Dustin J.
    Popovich, Phillip G.
    [J]. EXPERIMENTAL NEUROLOGY, 2008, 209 (02) : 378 - 388
  • [7] Brain dendritic cells and macrophages/microglia in central nervous system inflammation
    Fischer, HG
    Reichmann, G
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 166 (04) : 2717 - 2726
  • [8] Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii
    Fischer, HG
    Bonifas, U
    Reichmann, G
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (09) : 4826 - 4834
  • [9] FRIEDMAN B, 1995, J NEUROSCI, V15, P1044
  • [10] Early administration of IL-12 suppresses EAE through induction of interferon-γ
    Gran, B
    Chu, NS
    Zhang, GX
    Yu, S
    Li, YH
    Chen, XH
    Kamoun, M
    Rostami, A
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2004, 156 (1-2) : 123 - 131