Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice
Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice
复制标题
DOI：
10.1007/s00401-008-0476-x
复制
发表时间：
2009-03-01
影响因子：
12.7
通讯作者：
Yamazaki, Masashi
中科院分区：
文献类型：
--
作者：
Nishio, Yutaka;Koda, Masao;Yamazaki, Masashi
巨噬细胞移动抑制因子(MIF)是一种多潜能蛋白质，具有促炎症细胞因子、垂体激素和细胞增殖及迁移因子的作用。本研究的目的是利用雌性MIF基因敲除(KO)小鼠，阐明MIF在脊髓损伤(SCI)中的作用。采用静负荷(T8级，20g，5min)造成小鼠脊髓压迫性损伤。分析后肢运动功能，并进行组织学检查。KO组小鼠的后肢功能在损伤后三周开始显著恢复。甲酚紫染色显示，损伤后6周，KO组小鼠存活神经元数量明显多于WT组。免疫组织化学分析显示，脊髓损伤后24和72 h，KO组小鼠脑组织中Neun/caspase-3阳性、双阳性、凋亡的神经元数量明显少于WT组。这些结果与体外研究显示MIF-KO动物小脑颗粒神经元对谷氨酸神经毒性的抵抗力增加有关。这些结果表明，MIF的存在阻碍了脊髓损伤后神经元的存活。抑制MIF可能会减弱损伤脊髓的有害次级分子反应。
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.