Journal Article

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

Soon-Tae Lee, Kon Chu, Keun-Hwa Jung, Se-Jeong Kim, Dong-Hyun Kim, Kyung-Mook Kang, Nan Hyung Hong, Jin-Hee Kim, Jae-Joon Ban, Hee-Kwon Park, Seung U. Kim, Chung-Gyu Park, Sang Kun Lee, Manho Kim and Jae-Kyu Roh

in Brain

Published on behalf of The Guarantors of Brain

Volume 131, issue 3, pages 616-629
Published in print March 2008 | ISSN: 0006-8950
Published online December 2007 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awm306
Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke

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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-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB). 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.

Keywords: neural stem cell; spleen; cerebral inflammation; intracerebral haemorrhage; macrophage

Journal Article.  8898 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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