title: Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke.
abstract: Our previous findings showed 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 explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Microbiology and Biochemical Pharmaceutics, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: W W
authors.initials: WW
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Hospital of Integrated Traditional and Western Medicine in Shanxi, No 13, Fudong Road, Xinghualing District, Taiyuan, 030001 Shanxi, China.
authors.forename: C G
authors.initials: CG
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
authors.forename: L
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
authors.forename: C H
authors.initials: CH
authors.lastname: Jing
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
authors.forename: X M
authors.initials: XM
authors.lastname: Hua
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. Electronic address: lsting66@163.com.
authors.forename: S T
authors.initials: ST
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District,Shanghai 200092, China. Electronic address: rainy1208@126.com.
authors.forename: J
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002470:Cell Survival; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D007275:Injections, Intravenous; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
chemical_list: C486264:Cxcr4 protein, rat; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D019718:Receptors, CXCR4; D005472:Fluorouracil
keywords: 5-Fluorouracil; Bone marrow mononuclear cells; CXCR4; Growth factor; Stroke