Effects of umbilical cord blood monocytes transplantation on EPO protein and oligodendrocyte progenitors in neonatal rats with hypoxic-ischemic brain damage
JI Jia-Fen, ZHANG Jin-Ping, WANG Xiao-Li, MU Qing-Jie, FAN Meng-Meng, CHEN Yu-Xi
Department of Pediatrics, Clinical college, Weifang Medical University, Weifang, Shandong 261031, China
Abstract Objective To study the effects of umbilical cord blood monocytes (UCBMC) transplantation on erythropoietin (EPO) protein and oligodendrocyte progenitor cells in hypoxia-ischemia (HI) neonatal rats. Methods Forty seven-day-old Sprague-Dawley rats were randomly divided into normal control (N), HI, UCBMC and HI+UCBMC groups (n=10 each). Hypoxic-ischemic brain damage (HIBD) model was prepared according to the Rice method. Twenty-four hours after hypoxia, the N and HI groups were injected with 2 μL phosphate buffered saline (PBS), and the UCBMC and HI+UCBMC groups were injected with 3×106 UCBMC via the lateral ventricle. EPO protein and oligodendrocyte progenitor cells in the subventricular zone of the injured brain were observed by EPO/DAPI and NG2/DAPI immunofluorescence double staining, and their correlation was analyzed. Results Seven days after transplantation, there were more NG2+DAPI+ and EPO+DAPI+ cells in the HI+UCBMC group than in the UCBMC (P<0.05), N and HI groups (P<0.01). More NG2+DAPI+ and EPO+DAPI+ cells were observed in the UCBMC group compared with the N and HI groups (P<0.01). There were more NG2+DAPI+ cells in the N group than in the HI group (P<0.01). The number of NG2+DAPI+ cells was correlated with the number of EPO+DAPI+ cells in the HI+UCBMC group (r=0.898, β=1.4604, P<0.01). Conclusions UCBMC can promote expression of oligodendrocyte progenitor cells, which is correlated with an increase in EPO protein and thus repairs brain white matter damage in neonatal rats with HIBD.
JI Jia-Fen,ZHANG Jin-Ping,WANG Xiao-Li et al. Effects of umbilical cord blood monocytes transplantation on EPO protein and oligodendrocyte progenitors in neonatal rats with hypoxic-ischemic brain damage[J]. CJCP, 2013, 15(9): 775-778.
JI Jia-Fen,ZHANG Jin-Ping,WANG Xiao-Li et al. Effects of umbilical cord blood monocytes transplantation on EPO protein and oligodendrocyte progenitors in neonatal rats with hypoxic-ischemic brain damage[J]. CJCP, 2013, 15(9): 775-778.
Rothstein RP, Levison SW. Gray matter oligodendrocyte progenitors and neurons die caspase-3 mediated deaths subsequent to mild perinatal hypoxic/ischemic insults[J]. Dev Neurosci, 2005, 27(2-4): 149-159.
[2]
Dizon M, Szele F, Kessler JA. Hypoxia-ischemia induces an endogenous reparative response by local neural progenitors in the postnatal mouse telencephalon[J]. Dev Neurosci, 2010, 32(3):173-183.
[3]
Petersson KH, Pinar H, Stopa EG, Faris RA, Sadowska GB, Hanumara RC, et al. White matter injury after cerebral ischemia in ovine fetuses[J]. Pediatr Res, 2002, 51(6): 768-776.
Fan X, Heijnen CJ, van der KOOIJ MA, Groenendaal F, van Bel F. Beneficial effect of erythropoietin on sensorimotor function and white matter after hypoxia-ischemia in neonatal mice[J]. Pediatr Res, 2011, 69(1): 56-61.
[7]
Kako E, Kaneko N, Aoyama M, Hida H, Takebayashi H, Ikenaka K, et al. Subventricular zone-derived oligodendrogenesis in injured neonatal white matter in mice enhanced by a nonerythropoietic erythropoietin derivative[J]. Stem Cells, 2012, 30(10): 2234-2247.
[8]
Rice JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat[J]. Ann Neurol, 1981, 9(2): 131-141.
McTigue DM, Tripathi RB. The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem[J], 2008, 107(1): 1-19.
[12]
Dizon ML, Maa T, Kessler JA. The bone morphogenetic protein antagonist noggin protects white matter after perinatal hypoxia-ischemia[J]. Neurobiol Dis, 2011, 42(3): 318-326.
[13]
Kato S, Aoyama M, Kakita H, Hida H, Kato I, Ito T, et al. Endogenous erythropoietin from astrocyte protects the oligodendrocyte precursor cell against hypoxic and reoxygenation injury[J]. J Neurosci Res, 2011, 89(10):1566-1574.