title: In vivo two-photon imaging of axonal dieback, blood flow, and calcium influx with methylprednisolone therapy after spinal cord injury.
abstract: Severe spinal cord injury (SCI) can cause neurological dysfunction and paralysis. However, the early dynamic changes of neurons and their surrounding environment after SCI are poorly understood. Although methylprednisolone (MP) is currently the standard therapeutic agent for treating SCI, its efficacy remains controversial. The purpose of this project was to investigate the early dynamic changes and MP's efficacy on axonal damage, blood flow, and calcium influx into axons in a mouse SCI model. YFP H-line and Thy1-GCaMP transgenic mice were used in this study. Two-photon microscopy was used for imaging of axonal dieback, blood flow, and calcium influx post-injury. We found that MP treatment attenuated progressive damage of axons, increased blood flow, and reduced calcium influx post-injury. Furthermore, microglia/macrophages accumulated in the lesion site after SCI and expressed the proinflammatory mediators iNOS, MCP-1 and IL-1β. MP treatment markedly inhibited the accumulation of microglia/macrophages and reduced the expression of the proinflammatory mediators. MP treatment also improved the recovery of behavioral function post-injury. These findings suggest that MP exerts a neuroprotective effect on SCI treatment by attenuating progressive damage of axons, increasing blood flow, reducing calcium influx, and inhibiting the accumulation of microglia/macrophages after SCI.
authors.affiliation: Department of Orthopedics, the General Hospital of Chinese People's Liberation Army, Beijing, China, 100853.
authors.forename: Peifu
authors.initials: P
authors.lastname: Tang
authors.affiliation: 1] Department of Orthopedics, the General Hospital of Chinese People's Liberation Army, Beijing, China, 100853 [2] Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China, 518055.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Department of Orthopedics, the General Hospital of Chinese People's Liberation Army, Beijing, China, 100853 [2] Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China, 518055.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, the General Hospital of Chinese People's Liberation Army, Beijing, China, 100853.
authors.forename: Xinran
authors.initials: X
authors.lastname: Ji
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou, China, 73000.
authors.forename: Furong
authors.initials: F
authors.lastname: Ju
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China, 100069.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1] Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China, 518055 [2] Skirball Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, USA, 10016.
authors.forename: Wen-Biao
authors.initials: WB
authors.lastname: Gan
authors.affiliation: F.M. Kirby Program in Neuroscience, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA, 02115.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou, China, 73000.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China, 518055.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Orthopedics, the General Hospital of Chinese People's Liberation Army, Beijing, China, 100853.
authors.forename: Lihai
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008833:Microcirculation; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D017785:Photons; D012039:Regional Blood Flow; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D002154:Calpain; D053148:Caspase 3; C112682:Capn1 protein, mouse; D002118:Calcium; D008775:Methylprednisolone