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Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke

Cited 297 time in Web of Science Cited 325 time in Scopus
Authors
Lee, Soon-Tae; Chu, Kon; Jung, Keun-Hwa; Kim, Se-Jeong; Kim, Dong-Hyun; Kang, Kyung-Mook; Hong, Nan Hyung; Kim, Jin-Hee; Ban, Jae-Joon; Park, Hee-Kwon; Kim, Seung U; Park, Chung-Gyu; Lee, Sang Kun; Kim, Manho; Roh, Jae-Kyu
Issue Date
2007-12-25
Publisher
Oxford University Press
Citation
Brain. 2008 Mar;131(Pt 3):616-29. Epub 2007 Dec 20.
Keywords
AnimalsApoptosisBody Water/metabolismBrain/embryology/metabolismBrain Tissue Transplantation/*methodsCells, CulturedCoculture TechniquesDisease ProgressionEncephalitis/radiotherapy/*therapyFetal Stem Cells/transplantationFetal Tissue Transplantation/*methodsHumansInflammation Mediators/metabolismIntracranial Hemorrhages/complications/pathology/*therapyMacrophage ActivationMaleNeuronal PlasticityRatsRats, Sprague-DawleySplenectomyStem Cell Transplantation/*methodsStroke/etiology/pathology/therapy
Abstract
Neural stem cell (NSC) transplantation has been investigated as a means to reconstitute the damaged brain after stroke. In this study, however, we investigated the effect on acute cerebral and peripheral inflammation after intracerebral haemorrhage (ICH). NSCs (H1 clone) from fetal human brain were injected intravenously (NSCs-iv, 5 million cells) or intracerebrally (NSCs-ic, 1 million cells) at 2 or 24 h after collagenase-induced ICH in a rat model. Only NSCs-iv-2 h resulted in fewer initial neurologic deteriorations and reduced brain oedema formation, inflammatory infiltrations (OX-42, myeloperoxidase) and apoptosis (activated caspase-3, TUNEL) compared to the vehicle-injected control animals. Rat neurosphere-iv-2 h, but not human fibroblast-iv-2 h, also reduced the brain oedema and the initial neurologic deficits. Human NSCs-iv-2 h also attenuated both cerebral and splenic activations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-kappaB). However, we observed only a few stem cells in brain sections of the NSCs-iv-2 h group; in the main, they were detected in marginal zone of spleens. To investigate whether NSCs interact with spleen to reduce cerebral inflammation, we performed a splenectomy prior to ICH induction, which eliminated the effect of NSCs-iv-2 h transplantation on brain water content and inflammatory infiltrations. NSCs also inhibited in vitro macrophage activations after lipopolysaccharide stimulation in a cell-to-cell contact dependent manner. In summary, early intravenous NSC injection displayed anti-inflammatory functionality that promoted neuroprotection, mainly by interrupting splenic inflammatory responses after ICH.
ISSN
1460-2156 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18156155

http://brain.oxfordjournals.org/cgi/reprint/131/3/616.pdf

http://hdl.handle.net/10371/46139
DOI
https://doi.org/10.1093/brain/awm306
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College of Medicine/School of Medicine (의과대학/대학원)Microbiology (미생물학전공)Journal Papers (저널논문_미생물학전공)
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