title: Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy.
abstract: Cellular therapy with mesenchymal stem cells (MSCs) protects cortical neurons against hypoxic-ischemic injury of stroke. Although sorts of efforts have been made to confirm the neuroprotective effect of MSCs on neurons against hypoxic-ischemic injury, the mechanism is until now far away from clear. Here in this study, oxygen-glucose deprivation (OGD)-injured neuron model was applied to mimic the neuronal hypoxic-ischemic injury in vitro. Co-culturing with MSCs in a transwell co-culture system, the OGD injured neurons were rescued by 75.0 %. Further data demonstrated that co-culturing with MSCs protected the cortical neurons from the OGD-induced parthanatos by alleviating apoptosis-inducing factor (AIF) nuclear translocation; attenuated the neuronal necroptosis by down-regulating the expression of the two essential kinases in necroptosis, receptor interacting protein kinase1 (RIP1) and 3 (RIP3); rescued the neurons from apoptosis by deactivating caspase-3; whilst performed no significant influence on OGD-induced neuronal autophagy, according to its failed regulation on Beclin1. In conclusion, MSCs potentially protect the cortical neurons from OGD-injury in vitro, through rescuing neurons from the cell death of parthanatos, necroptosis, and apoptosis, but not autophagy, which could provide some evidence to the mechanism explanation on stem cell treatment for ischemic stroke.
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.|Department of Neurology, The Affiliated Ruikang Hospital of Guangxi Traditional Chinese Medical University, Nanning, 530011, Guangxi Zhuang Autonomous Region, China.
authors.forename: Deyan
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.|Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
authors.forename: Juehua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
authors.forename: Lily
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Affiliated Ruikang Hospital of Guangxi Traditional Chinese Medical University, Nanning, 530011, Guangxi Zhuang Autonomous Region, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Luo
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.|Department of Neurology, Affiliated Hospital of Hainan Medical College, Haikou, 570102, Hainan, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Qijin
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China. xfliu2@vip.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Apoptosis; Autophagy; Ischemic stroke; Mesenchymal stem cells (MSCs); Necroptosis; Parthanatos