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Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1alpha stabilization in the host brain

Cited 43 time in Web of Science Cited 49 time in Scopus
Authors
Chu, Kon; Jung, Keun-Hwa; Kim, Se-Jeong; Lee, Soon-Tae; Kim, Juhyun; Park, Hee-Kwon; Song, Eun-Cheol; Kim, Seung U; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu
Issue Date
2008-03-29
Publisher
Elsevier
Citation
Brain Res. 1207, 182-192
Keywords
AnimalsBrain/metabolism/surgeryBrain Infarction/prevention & controlBrain Ischemia/pathology/prevention & control/*surgeryChemokine CXCL12/pharmacologyCyclooxygenase 2/metabolismDeferoxamine/pharmacologyDisease Models, AnimalDose-Response Relationship, DrugFlow Cytometry/methodsGene Expression Regulation/drug effectsHumansHypoxia-Inducible Factor 1, alpha Subunit/drug effects/*metabolismNeurons/drug effects/*physiologyRatsReceptors, CXCR4/metabolismSiderophores/pharmacologyStem Cell Transplantation/*methodsStem Cells/drug effects/*physiologyTime FactorsUp-Regulation/physiologyVascular Endothelial Growth Factor A/metabolism
Abstract
Hypoxia-inducible factor-1 (HIF-1) plays important roles in the prevention of cerebral ischemia. Deferoxamine (DFX), an iron chelator stabilizes the HIF-1alpha and activates target genes involved in compensation for ischemia. In this study, we are to investigate whether HIF-1alpha can be stabilized in human neural stem cells (NSCs) by DFX, and pre-transplantation of NSCs with HIF-1alpha stabilization can induce prolonged ischemic tolerance. In the DFX-treated NSCs, the HIF-1alpha protein expression was increased about 100-fold time-dependently, and subsequent transcriptional activation (VEGF, BDNF and CXCR4) was also observed. To test an ability to induce ischemic prevention in vivo, DFX-treated NSCs or naive NSCs were transplanted in the striatum of adult rats. Seven days following the transplantation, focal cerebral ischemia was done. Infarct volumes were reduced in both NSCs-transplanted groups, compared with ischemia-only, but more reduced in DFX-treated NSCs group. The protective effects of NSCs were ablated when HIF-1alpha was silenced. HIF-1alpha protein levels were increased in both NSCs-transplanted groups, but more increased in DFX-treated NSCs group. RT-PCR analysis manifested a downregulation of mRNA expression of TNF-alpha, IL-6 and MMP-9 in both NSCs groups, but further decrease in DFX-treated NSCs group. These findings provide evidence that HIF-1alpha stabilization in human NSCs can be achieved effectively by DFX, and HIF-1alpha-stabilized NSCs protect against ischemia in a preventive mode.
ISSN
0006-8993 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18371939

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6SYR-4S01WNN-4-N&_cdi=4841&_user=168665&_orig=search&_coverDate=05%2F01%2F2008&_sk=987929999&view=c&wchp=dGLbVzz-zSkWz&md5=0cd6644708b4640eb9a9b536aa3179cb&ie=/sdarticle.pdf

http://hdl.handle.net/10371/67831
DOI
https://doi.org/10.1016/j.brainres.2008.02.043
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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