Asan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea.
Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.
Int J Mol Sci. 2022 Jun 23;23(13):6975. doi: 10.3390/ijms23136975.
The mechanism of the neuroprotective effect of the macrophage migration inhibitory factor (MIF) in vivo is unclear. We investigated whether the MIF promotes neurological recovery in an in vivo mouse model of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) surgery was performed to make ischemic stroke mouse model. Male mice were allocated to a sham vehicle, a sham MIF, a middle cerebral artery occlusion (MCAO) vehicle, and MCAO+MIF groups. Transient MCAO (tMCAO) was performed in the MCAO groups, and the vehicle and the MIF were administered via the intracerebroventricular route. We evaluated the neurological functional scale, the rotarod test, and T2-weighted magnetic resonance imaging. The expression level of the microtubule-associated protein 2 (MAP2), Bcl2, and the brain-derived neurotrophic factor (BDNF) were further measured by Western blot assay. The Garcia test was significantly higher in the MCAO+MIF group than in the MCAO+vehicle group. The MCAO+MIF group exhibited significantly better performance on the rotarod test than the MCAO+vehicle group, which further had a significantly reduced total infarct volume on T2-weighted MRI imaging than the MCAO vehicle group. Expression levels of BDNF, and MAP2 tended to be higher in the MCAO+MIF group than in the MCAO+vehicle group. The MIF exerts a neuroprotective effect in an in vivo ischemic stroke model. The MIF facilitates neurological recovery and protects brain tissue from ischemic injury, indicating a possibility of future novel therapeutic agents for stroke patients.
巨噬细胞移动抑制因子（MIF）在体内的神经保护作用机制尚不清楚。我们研究了 MIF 是否能促进体内缺血性中风小鼠模型的神经恢复。通过短暂性大脑中动脉闭塞（MCAO）手术制作缺血性中风小鼠模型。雄性小鼠被分为假手术对照组、假 MIF 组、MCAO 对照组和 MCAO+MIF 组。MCAO 组进行短暂性 MCAO（tMCAO），通过脑室内途径给予载体和 MIF。我们评估了神经功能量表、转棒试验和 T2 加权磁共振成像。进一步通过 Western blot 测定微管相关蛋白 2（MAP2）、Bcl2 和脑源性神经营养因子（BDNF）的表达水平。Garcia 测试评分在 MCAO+MIF 组明显高于 MCAO+载体组。MCAO+MIF 组在转棒试验中的表现明显优于 MCAO+载体组，T2 加权 MRI 成像显示总梗死体积明显小于 MCAO 载体组。MCAO+MIF 组的 BDNF 和 MAP2 表达水平均高于 MCAO+载体组。MIF 在体内缺血性中风模型中发挥神经保护作用。MIF 促进神经恢复并保护脑组织免受缺血性损伤，这表明它有可能成为未来治疗中风患者的新药物。
