经脑室神经干细胞移植对脑室周围白质软化新生大鼠的脑病理评估

Cerebral pathological evaluation following neural stem cells intraventricular transplantation in neonatal rats with periventricular leukomalacia

目的对经脑室植入神经干细胞（NSCs）的脑室周围白质软化（Periventricular leukolamacia，PVL）新生大鼠进行光镜下脑病理评估，探讨NSCs移植对治疗早产儿PVL的可行性。方法采用E14胎鼠大脑皮层制备NSCs。2日龄新生大鼠随机分为PVL对照组（PVL组），PVL＋DMEM／F12培养基对照组（PVL＋DMEM／F12组），PVL＋神经干细胞（NSCs）移植组（PVL＋NSCs组），假手术对照组（Sham组），Sham＋DMEM／F12培养基对照组（Sham＋DMEM/F12组），Sham＋NSCs移植组（Sham＋NSCs组），每组18～21只。对2日龄PVL新生大鼠在建模后72h进行经脑室NSCs移植，分别于移植后7，14，21d进行光镜下脑病理评估。结果随着移植后时间的增加，脑白质病变呈进一步改善。移植后21d光镜下病理证实，未移植组脑白质呈轻度和重度病变各占50％，神经元病理评分为1．28±0．86。移植组则有30％白质完全正常，轻度和重度病变各占40％和30％，神经元病理评分为0．32±0．16，两组在脑白质病变程度以及神经元病理评分之间的差异均呈非常显著性意义（x^2=10．7，P〈0．01；F=29．664，P〈0．01）。结论经脑室外源性NSCs移植可明显改善脑白质的病理损伤。经脑室NSCs移植对早产儿PVL具有很大的治疗潜力，为今后成功防治早产儿这一最常见的脑损伤顽症提供了新的可行性途径。

Objective To evaluate the brain pathological changes following exdogenous neural stem cells （NSCs） intraventrilar transplantation in neonatal rats with periventricular leukomalacia （ PVL）, and to explore the feasibility of NSCs transplantation for the treatment of PVL in premature infants. Methods NSCs were prepared from El4 embryonic rat brain. Two-day-old neonatal rats were randomly divided into six groups： PVL, PVL ＋ culture medium, PVL ＋ NSCs, sham operation, sham operation ＋ culture medium, and sham operation ＋ NSCs （ 18-21 rats each group）. Intraventricular transplantation of exdogenous NSCs was performed 72 hrs after PVL induction or sham operation. The cerebral pathological evaluation was undertaken by light microscopy 7, 14 and 21 days after transplantation. Results The pathological changes in the cerebral white matter were gradually improved with the prolonged time after transplantation. After 21 days of transplantation, 50% of the cerebral white matter showed mild pathological changes and 50% of that showed severe pathological changes, with neuronal pathological scores of 1.28 ± 0. 86, in the untreated PVL group. In the PVL ＋ NSCs group, 30% of normal white matter, 40% of mild and 30% of severe pathological changes in the white matter were observed, with neuronal pathological scores of 0. 32 ± 0. 16, 21 days after transplantation. There were very significant differences in both of pathological changes in the cerebral white matter and neuronal pathologicalscores between the PVL and PVL ＋ NSCs groups （ X^2 = 10.7, P 〈 0.01 ; F= 29. 664, P 〈 0.01 ）. Conclusions Intraventricular transplantation of exdogenous NSCs can apparently improve cerebral white matter damage. It is suggested that intraventricular transplantation of NSCs is of a great potential feasibility for the treatment of PVL in premature infants.