title: Neuroprotection by intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats in a model of ischemic stroke.
abstract: Our previous studies showed that bone marrow mononuclear cells (BMMNCs) from 5-fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to further explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in the same model. Rats were intravenously pre-treated with 5-FU, and BMRMNCs were collected 7 days later and subjected to flow cytometry for detection of CD34, CD45 and CD90. Middle cerebral artery occlusion (MCAO) was induced in rats, and BMMNCs and BMRMNCs were independently transplanted via the tail vein at 24 h after MCAO. NISSL staining was performed 14 days after cell transplantation and the viable cells in the hippocampus were counted. Stromal cell-derived factor 1 (SDF-1) mRNA expression was detected in the penumbra at 7 and 14 days after treatment. The contents of pro-inflammatory cytokines and growth factors as well as microvessel density (MVD) were determined at 14 days. Results showed more BMRMNCs were positive for CD34, CD45 and CD90. After transplantation, more viable cells were observed in the hippocampus of BMRMNCs treated rats. In addition, BMRMNCs transplantation significantly increased MVD, reduced pro-inflammatory cytokines and raised growth factors in the penumbra. However, the SDF-1 mRNA expression was comparable between BMRMNCs group and BMMNCs group. Our results indicate that BMRMNCs are likely to more effectively improve the local microenvironment to increase viable cells and elevate angiogenesis, exerting neuroprotective effects on cerebral ischemia in rats.
authors.affiliation: a Department of Neurosurgery, School of Medicine, Xinhua Hospital , Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Anatomy and Embryology , School of Basic Medical Sciences, Peking University Health Science Center , Beijing , China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: c Laboratory of Microbiology and Biochemical Pharmaceutics, School of Pharmacy , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: c Laboratory of Microbiology and Biochemical Pharmaceutics, School of Pharmacy , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Mao
authors.affiliation: a Department of Neurosurgery, School of Medicine, Xinhua Hospital , Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Hua
authors.affiliation: d Department of Ultrasound, School of Medicine, Xinhua Hospital , Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD; D002545:Brain Ischemia / Q000150:complications; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D055806:Microvessels / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000601:surgery*
chemical_list: D015703:Antigens, CD; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D005472:Fluorouracil
keywords: 5-fluorouracil; Bone marrow mononuclear cells; Growth factor; Microvessel density; Stroke