title: MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury.
abstract: Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI.
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Chemistry, College of Pharmacy, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Donghe
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Neurobiology, Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Basic Medical Sciences, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Chenyuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Sciences, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Tianchen
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Zhanghui
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000032:analysis / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D015032:Zinc; D008775:Methylprednisolone