Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice.
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.
Nishio
Yutaka
Y
Department of Orthopaedic Surgery, Chiba University, Chuo-ku, Japan.
Koda
Masao
M
Hashimoto
Masayuki
M
Kamada
Takahito
T
Koshizuka
Shuhei
S
Yoshinaga
Katsunori
K
Onodera
Shin
S
Nishihira
Jun
J
Okawa
Akihiko
A
Yamazaki
Masashi
M
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
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