Laboratory for Experimental Brain Research, Department of Clinical Sciences, Lund University, BMC A13, 22184 Lund, Sweden.
J Neuroinflammation. 2011 Jun 29;8:75. doi: 10.1186/1742-2094-8-75.
Macrophage migration inhibitory factor (MIF) has been proposed to play a detrimental role in stroke. We recently showed that MIF promotes neuronal death and aggravates neurological deficits during the first week after experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied the putative role of MIF in post-stroke inflammation.
We subjected C57BL/6 mice, Mif-/- (MIF-KO) or Mif+/+ (WT), to a transient occlusion of the right middle cerebral artery (tMCAo) or sham-surgery. We studied MIF expression, GFAP expression and the number of CD74-positive cells in the ischemic brain hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-α protein levels in the brain (48 h after surgery) and serum (48 h and 7 days after surgery) by a multiplex immunoassay.
We observed that MIF accumulates in neurons and astrocytes of the peri-infarct region, as well as in microglia/macrophages of the infarct core up to 7 days after stroke. Among the inflammatory mediators analyzed, we found a significant increase in cerebral IL-12 and KC levels after tMCAo, in comparison to sham-surgery. Importantly, the deletion of Mif did not significantly affect the levels of the cytokines evaluated, in the brain or serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and the number of MIF receptor (CD74)-positive cells within the ischemic brain hemisphere did not differ significantly between WT and MIF-KO mice subjected to tMCAo.
We conclude that MIF does not affect major components of the inflammatory/immune response during the first week after experimental stroke. Based on present and previous evidence, we propose that the deleterious MIF-mediated effects in stroke depend primarily on an intraneuronal and/or interneuronal action.
巨噬细胞移动抑制因子（MIF）被认为在中风中起有害作用。我们最近表明，MIF 在实验性中风后的第一周内促进神经元死亡并加重神经功能缺损，在小鼠中。由于 MIF 调节组织炎症，我们研究了 MIF 在中风后炎症中的潜在作用。
我们使 C57BL/6 小鼠、Mif-/-（MIF-KO）或 Mif+/+（WT）接受右侧大脑中动脉短暂闭塞（tMCAo）或假手术。我们使用主要的免疫组织化学方法在 tMCAo 后 7 天研究缺血半球中的 MIF 表达、GFAP 表达和 CD74 阳性细胞的数量。我们通过多重免疫测定法在大脑（手术后 48 小时）和血清（手术后 48 小时和 7 天）中测定 IFN-γ、IL-2、IL-4、IL-5、IL-10、IL-12、KC/CXCL-1 和 TNF-α 蛋白水平。
我们观察到，MIF 在梗塞核心区的神经元和星形胶质细胞中以及梗塞核心区的小胶质细胞/巨噬细胞中积聚，直至中风后 7 天。在所分析的炎症介质中，与假手术相比，我们发现 tMCAo 后大脑中 IL-12 和 KC 水平显著增加。重要的是，Mif 的缺失并没有显著影响大脑或血清中评估的细胞因子水平。此外，tMCAo 后 48 小时和 7 天，WT 和 MIF-KO 小鼠的脾脏重量相似。最后，WT 和 MIF-KO 小鼠的缺血半球内 GFAP 免疫反应性的程度和 MIF 受体（CD74）阳性细胞的数量没有显著差异。
我们得出结论，MIF 不会影响实验性中风后第一周内炎症/免疫反应的主要成分。基于目前和以前的证据，我们提出 MIF 在中风中的有害介导作用主要取决于神经元内和/或神经元间的作用。
