Absence of IL-1β positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury.

Absence of IL-1β positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury.
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DOI:
10.1186/1742-2094-10-6
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发表时间:
2013-01-14
影响因子:
9.3
通讯作者:
Hendrix S
Hendrix S
中科院分区:
医学1区
文献类型:
--
作者:
Boato F;Rosenberger K;Nelissen S;Geboes L;Peters EM;Nitsch R;Hendrix S

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神经和免疫系统之间的精确串扰对于损伤后的神经保护和轴突可塑性是重要的。最近,我们证明IL-1β在体外可作为器官型脑切片神经突起生长的有效诱导剂,提示IL-1β在轴突可塑性中的潜在功能。在此,我们研究了IL-1β在胶质瘢痕形成过程中对轴突可塑性的影响,以及在脊髓压迫损伤(SCI)小鼠模型中对功能恢复的影响。我们使用IL-1β缺乏模型(IL-1βKO小鼠)并给予重组IL-1β。与我们的假设相反,组织学分析显示局部应用重组IL-1β后,病变宽度显著增加,病变中心尾侧皮质脊髓束纤维数量减少。一致地,与PBS对照相比,治疗显著恶化了小鼠SCI后的神经学结果。相比之下,与野生型小鼠相比,IL-1βKO小鼠中缺乏IL-1β显著改善了SCI的恢复。组织学分析显示,与对照组相比,IL-1βKO小鼠的病变尺寸更小,病变宽度减少,白色物质中的星形胶质细胞增生大大减少,而病变尾部5 mm处的皮质脊髓束纤维数量显著增加。我们的研究首次描述了IL-1β不仅对损伤发展(在大小和胶质细胞活化方面),而且对损伤后中枢神经系统轴突可塑性的有害影响。
Precise crosstalk between the nervous and immune systems is important for neuroprotection and axon plasticity after injury. Recently, we demonstrated that IL-1β acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1β in axonal plasticity. Here, we have investigated the effects of IL-1β on axon plasticity during glial scar formation and on functional recovery in a mouse model of spinal cord compression injury (SCI). We used an IL-1β deficiency model (IL-1βKO mice) and administered recombinant IL-1β. In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1β in IL-1βKO mice significantly improved recovery from SCI compared with wildtype mice. Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.
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