title: Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Chiba University, Chuo-ku, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishio
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Takahito
authors.initials: T
authors.lastname: Kamada
authors.forename: Shuhei
authors.initials: S
authors.lastname: Koshizuka
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Shin
authors.initials: S
authors.lastname: Onodera
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D002531:Cerebellum / Q000473:pathology; D004268:DNA-Binding Proteins; D005121:Extremities / Q000503:physiopathology; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D008124:Locomotion; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D020127:Recovery of Function; D013117:Spinal Cord Compression / Q000150:complications; D013119:Spinal Cord Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D008263:Macrophage Migration-Inhibitory Factors; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D018698:Glutamic Acid; D053148:Caspase 3