title: Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte.
abstract: Mesenchymal stem cell (MSC) transplantation reduces the neurological impairment caused by hypoxic-ischemic brain damage (HIBD) via immunomodulation. In the current study, we found that MSC transplantation improved learning and memory function and enhanced long-term potentiation in neonatal rats subjected to HIBD and the amount of IL-6 released from MSCs was far greater than that of other cytokines. However, the neuroprotective effect of MSCs infected with siIL-6-transduced recombinant lentivirus (siIL-6 MSCs) was significantly weakened in the behavioural tests and electrophysiological analysis. Meanwhile, the hippocampal IL-6 levels were decreased following siIL-6 MSC transplantation. In vitro, the levels of IL-6 release and the levels of IL-6R and STAT3 expression were increased in both primary neurons and astrocytes subjected to oxygen and glucose deprivation (OGD) following MSCs co-culture. The anti-apoptotic protein Bcl-2 was upregulated and the pro-apoptotic protein Bax was downregulated in OGD-injured astrocytes co-cultured with MSCs. However, the siIL-6 MSCs suppressed ratio of Bcl-2/Bax in the injured astrocytes and induced apoptosis number of the injured astrocytes. Taken together, these data suggest that the neuroprotective effect of MSC transplantation in neonatal HIBD rats is partly mediated by IL-6 to enhance anti-apoptosis of injured astrocytes via the IL-6/STAT3 signaling pathway.
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Stem Cell Therapy Engineering Technical Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Stem Cell Therapy Engineering Technical Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Mulan
authors.initials: M
authors.lastname: He
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Stem Cell Therapy Engineering Technical Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Stem Cell Therapy Engineering Technical Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Jinngjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing 400014, China.
authors.forename: Nali
authors.initials: N
authors.lastname: Hou
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Tan
authors.initials: T
authors.lastname: Bin
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Stem Cell Therapy Engineering Technical Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing 400014, China.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Chongqing Stem Cell Therapy Engineering Technical Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D001522:Behavior, Animal; D018920:Coculture Techniques; D003071:Cognition; D015870:Gene Expression; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism* / Q000523:psychology / Q000628:therapy; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007858:Learning; D008568:Memory; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014161:Transduction, Genetic; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D051028:bcl-2-Associated X Protein