title: Comparison of the therapeutic effects of bone marrow mononuclear cells and microglia for permanent cerebral ischemia.
abstract: In this study we transplanted bone marrow mononuclear cells (BM-MNCs) or microglia into rats that had undergone permanent cerebral ischemia and observed the distribution or morphology of transplanted cells in vivo. In addition, we compared the effects of BM-MNCs and microglia on infarct volume, brain water content, and functional outcome after permanent cerebral ischemia. BM-MNCs and microglia were obtained from femur and brain, respectively, of newborn rats. Adult rats were injected with vehicle or 3 million BM-MNCs or microglia via the tail vein 24h after permanent middle cerebral artery occlusion (pMCAO). The distribution or morphologic characteristics of transplanted BM-MNCs (double stained with BrdU/Cd34 or BrdU/CD45) and microglia (double stained with BrdU/Iba-1) were detected with immunofluorescent staining at 3 or 7 and 14 days after pMCAO. Functional deficits were assessed by the modified neurologic severity score at 1, 3, 7 and 14 days after pMCAO. Brain water content was assessed at 3 days, and infarct volume was determined at 14 days. We observed more BrdU/CD45 and BrdU/Iba-1 double-stained cells than BrdU/CD34 double-stained cells around the infarcted area. Some infused microglia showed the morphology of innate microglia at 7 days after pMCAO, and the number increased at 14 days. BM-MNC-treated rats showed significantly reduced infarct volume and brain water content compared to vehicle- and microglia-treated rats. In addition, BM-MNC treatment reduced neurologic deficit scores compared to those in the other groups. The results provide evidence that infusion of BM-MNCs, but not microglia, is neuroprotective after permanent cerebral ischemia.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Lie
authors.initials: L
authors.lastname: Yu
authors.forename: Chunying
authors.initials: C
authors.lastname: Ou
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D001929:Brain Edema / Q000209:etiology / Q000628:therapy; D020520:Brain Infarction / Q000209:etiology / Q000628:therapy; D002545:Brain Ischemia / Q000601:surgery*; D001973:Bromodeoxyuridine; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000502:physiology* / Q000637:transplantation; D009000:Monocytes / Q000502:physiology* / Q000637:transplantation; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C100745:Aif1 protein, rat; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D001973:Bromodeoxyuridine