TY - JOUR
T1 - Comparison of the therapeutic effects of bone marrow mononuclear cells and microglia for permanent cerebral ischemia
AU - Jiang, Chao
AU - Wang, Jianping
AU - Yu, Lie
AU - Ou, Chunying
AU - Liu, Xi
AU - Zhao, Xiaochun
AU - Wang, Jian
N1 - Funding Information:
This work was supported by grants from Medical Science and Technology Research Programs of Henan Province ( WKJ2010-2-016 ), the Overseas Training Program of Henan Province Medical Academic Leaders ( 2011023 ), AHA ( 09BGIA2080137 ), and NIH ( K01AG031926 , R01AT007317 , R01NS078026 ). We thank Claire Levine for assistance with this manuscript.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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 also 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 24. h after permanent middle cerebral artery occlusion (pMCAO). The distribution or morphologic characteristics of transplanted BM-MNCs (BrdU/double-stained CD34 and CD45) and microglia (BrdU/double-stained 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 with dry-wet weight method at 3 days, and infarct volume was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 14 days. More BrdU/double-stained CD45- and Iba-1-positive cells were observed than BrdU/double-stained CD34-positive 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.
AB - 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 also 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 24. h after permanent middle cerebral artery occlusion (pMCAO). The distribution or morphologic characteristics of transplanted BM-MNCs (BrdU/double-stained CD34 and CD45) and microglia (BrdU/double-stained 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 with dry-wet weight method at 3 days, and infarct volume was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 14 days. More BrdU/double-stained CD45- and Iba-1-positive cells were observed than BrdU/double-stained CD34-positive 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.
KW - Bone marrow mononuclear cells
KW - Cerebral ischemia
KW - Microglia
KW - Therapeutic effect
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U2 - 10.1016/j.bbr.2013.05.011
DO - 10.1016/j.bbr.2013.05.011
M3 - Article
C2 - 23685323
AN - SCOPUS:84878678001
SN - 0166-4328
VL - 250
SP - 222
EP - 229
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -