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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 47 time in
Web of Science
Cited 53 time in Scopus
- Authors
- Issue Date
- 2008-03-29
- Publisher
- Elsevier
- Citation
- Brain Res. 1207, 182-192
- Keywords
- Animals ; Brain/metabolism/surgery ; Brain Infarction/prevention & control ; Brain Ischemia/pathology/prevention & control/*surgery ; Chemokine CXCL12/pharmacology ; Cyclooxygenase 2/metabolism ; Deferoxamine/pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Flow Cytometry/methods ; Gene Expression Regulation/drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects/*metabolism ; Neurons/drug effects/*physiology ; Rats ; Receptors, CXCR4/metabolism ; Siderophores/pharmacology ; Stem Cell Transplantation/*methods ; Stem Cells/drug effects/*physiology ; Time Factors ; Up-Regulation/physiology ; Vascular 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
https://hdl.handle.net/10371/67831
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