Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia.

Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia.
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DOI:
10.1177/0963689718781330
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发表时间:
2018-07
影响因子:
3.3
通讯作者:
Kim YB
Kim YB
中科院分区:
医学4区
文献类型:
--
作者:
Kim TK;Park D;Ban YH;Cha Y;An ES;Choi J;Choi EK;Kim YB

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在实验性脑室周围白质软化(PVL)模型中研究了人少突胶质细胞祖细胞(F3.olig2)对神经行为缺陷的改善作用。对7日龄雄性大鼠进行缺氧-缺血-脂多糖注射(HIL),并在出生后第10天(PND)脑室内移植F3.olig2(4 × 105个细胞/大鼠)一次或在PND 10、17、27和37重复。在PND 14、20、30和40通过柱体试验、自发活动和旋转棒性能评价神经行为障碍,并在PND 41 -45通过被动回避和Morris水迷宫性能评价认知功能。F3.olig2细胞恢复了受损大脑对侧前肢的使用率,改善了运动活性,并恢复了PVL动物的转棒性能;此外,观察到学习和记忆功能的显著改善。结果表明,移植的F3·olig 2细胞可迁移至损伤区,成熟为表达髓鞘碱性蛋白(MBP)的少突胶质细胞,并明显减轻了胼胝体中宿主MBP的丢失。结果表明,移植的F3.olig2细胞通过防止轴突脱髓鞘恢复神经行为功能,并且人少突胶质细胞祖细胞可以作为围产期缺氧缺血性和感染性脑损伤(包括PVL和脑瘫)的细胞治疗的候选者。
The effects of human oligodendrocyte progenitor (F3.olig2) cells on improving neurobehavioral deficits were investigated in an experimental model of periventricular leukomalacia (PVL). Seven-day-old male rats were subjected to hypoxia-ischemia-lipopolysaccharide injection (HIL), and intracerebroventricularly transplanted with F3.olig2 (4 × 105 cells/rat) once at post-natal day (PND) 10 or repeatedly at PND10, 17, 27, and 37. Neurobehavioral disorders were evaluated at PND14, 20, 30, and 40 via cylinder test, locomotor activity, and rotarod performance, and cognitive function was evaluated at PND41–45 through passive avoidance and Morris water-maze performances. F3.olig2 cells recovered the rate of use of the forelimb contralateral to the injured brain, improved locomotor activity, and restored rotarod performance of PVL animals; in addition, marked improvement of learning and memory function was seen. It was confirmed that transplanted F3·olig2 cells migrated to injured areas, matured to oligodendrocytes expressing myelin basic protein (MBP), and markedly attenuated the loss of host MBP in the corpus callosum. The results indicate that the transplanted F3.olig2 cells restored neurobehavioral functions by preventing axonal demyelination, and that human oligodendrocyte progenitor cells could be a candidate for cell therapy of perinatal hypoxic-ischemic and infectious brain injuries including PVL and cerebral palsy.
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