Effects of human umbilical cord mesenchymal stem cells intervention on glial cells and neurobehavior in the newborn rat model of white matter damage / 中华围产医学杂志

ABSTRACT

Objective To investigate the alterations in oligodendrocyte and microglia and changes in neurobehavior after human umbilical cord mesenchymal stem cells (HUcMSCs) intervention on the newborn rat model of white matter damage (WMD) induced by hypoxia-ischemia.Methods After the operation of left common carotid artery ligation and 4 h hypoxia (6％ O2 and 94％ N2),twelve three-day-old Sprague-Dawley rats died and the remaining sixty rats were randomly divided into the experimental group and the control group.The first day was 0 to 24 h after birth.Rats of the experimental group were intraperitoneally injected the fourth generation HUcMSCs 1 × 106 (0.05 ml) on the third,fourth and fifth day respectively.At the same time,rats of the control group were intraperitoneally injected phosphate buffer (0.05 ml).Eight rats of each group were executed on the tenth and twenty first day respectively to detect the number of cells positive for myelin basic protein (MBP) and ectodermal dysplasia-1 (ED-1) staining by immunohistochemistry.Three rats of each group were executed on the tenth and twenty first day respectively to detect MBP and ED-1 expression by western blot.Eight rats of each group were weighed and underwent the neurobehavioral evaluation on the twenty eighth day.Data were analyzed using t test.Results On the tenth and twenty first day,the numbers of MBP-positive cells in the experimental group (11.8 ± 4.1 and 23.8± 8.1) were significantly higher than those in the control group (6.7±3.1 and 11.5 ± 5.8,t=-2.81 and 3.49,both P＜0.05) ; and the numbers of ED-1 positive cells in the experimental group (20.8 ± 3.4 and 19.1 ± 2.8) were significantly lower than those in the control group (32.8±4.2 and 29.5±5.2,t=6.23 and 4.93,both P＜0.01).On the tenth and twenty first day,MBP expressions in the experimental group (1.3 ± 0.1 and 1.1 ± 0.1) were higher than those in the control group (0.8±0.0 and 0.6±0.1,t=-7.53 and 6.68,both P＜0.01) ; and the ED-1 expressions in the experimental group (0.6±0.1 and 0.4±0.1) were lower than those in the control group (1.0±0.1 and 0.8±0.1,t=3.09 and 4.90,both P＜0.01).Weight on the seventh,tenth,fourteenth,twenty first and twenty eighth day in the experimental group [(15.0± 1.2),(16.6±0.9),(27.0± 1.6),(44.2±2.3) and (68.1 ±4.2) g] was significantly higher than that in the control group [(12.7 ± 1.6),(13.5 ± 2.0),(23.6 ± 1.9),(38.4± 0.9) and (60.0± 4.2) g,t=-3.11,-3.97,3.67,-6.52 and-3.72,all P＜0.05].On the twenty eighth day,the score of open field test in the experimental group was significantly higher than that in the control group (36.5 ± 2.9 vs 24.3 ± 3.6,t=7.36,P＜0.01).So was the hanging test (3.6± 1.0 vs 2.0±0.7,t=3.53,P＜0.01).In Cylinder test,the ratio of left/both and right/both forefeet in the experimental group were similar [(49.8± 13.3) ％ vs (41.4±5.9) ％,t=0.86,P＞0.05],but the ratio of left/both forefeet in the control group was higher than right/both [(49.5 ± 11.3) ％ vs (31.2±3.2) ％,t=4.38,P＜0.01].Conclusions HUcMSCs are able to enhance the number of oligodendrocytes while weaken the activity of microglias in the WMD newborn rat model,and to promote the physical development and improve the rat neurobehavior.