title: In vivo two-photon imaging reveals a role of progesterone in reducing axonal dieback after spinal cord injury in mice.
abstract: Progesterone (PG) as a neuroprotective reagent has been used for the treatment of spinal cord injury (SCI) in experimental animal models. However, its effect and mechanism on axonal dieback at the early stage of SCI remain unclear. Here, we investigate the dynamics of injured axons and the effect of PG on the axonal dieback, glial response, and behavioral recovery in a mouse model of SCI. Two-photon intravital imaging combined with a simplified imaging window chamber were used to image axons in hemisected spinal cords over a period of 3 days. Repeated imaging showed that axonal dieback distance in mice treated with PG after SCI was significantly reduced than that in mice treated with vehicle after SCI (P < 0.05) at the time point of 24 h, 48 h, and 72 h after SCI. The densities of astrocytes and microglia in the SCI-vehicle treated group were significantly higher than those in mice treated with PG after SCI (P < 0.05). Real time polymerase chain reaction assay indicated that administration of PG after SCI down-regulated the expression of pro-inflammatory cytokines MCP-1, NOS2, and IL-1β (P < 0.05). PG treatment also improved the behavioral performance post injury. These findings suggested that PG exerted a neuroprotective effect by attenuating axonal dieback, reducing the accumulation of astrocytes and microglia and inhibiting the release of pro-inflammatory cytokines.
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China; School of Life Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Xie
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Ju
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Akbar
authors.initials: A
authors.lastname: Khan
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address: sxzhang@lzu.edu.cn.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001369:Axons / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D008297:Male; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D011374:Progesterone
keywords: Axonal dieback; Inflammation; Microglia; Progesterone; Spinal cord injury; Two-photon imaging