title: Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke.
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.
authors.affiliation: Stroke & Stem Cell Laboratory, Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Kyung-Mook
authors.initials: KM
authors.lastname: Kang
authors.forename: Nan Hyung
authors.initials: NH
authors.lastname: Hong
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Ban
authors.forename: Hee-Kwon
authors.initials: HK
authors.lastname: Park
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D000818:Animals; D017209:Apoptosis; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism; D016380:Brain Tissue Transplantation / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D004660:Encephalitis / Q000532:radiotherapy / Q000628:therapy*; D053686:Fetal Stem Cells / Q000637:transplantation; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020300:Intracranial Hemorrhages / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008262:Macrophage Activation; D008297:Male; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013156:Splenectomy; D033581:Stem Cell Transplantation / Q000379:methods*; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000628:therapy
chemical_list: D018836:Inflammation Mediators