立体定向脑内移植神经干细胞改善颅脑损伤大鼠的神经运动功能

摘要

背景：细胞替代治疗是重建受损神经系统组织结构，恢复神经系统功能的一种有效策略，具有极为广阔的应用前景。　　目的：探讨立体定向脑内移植神经干细胞对颅脑损伤大鼠神经运动功能的影响。　　方法：将20只雄性SD大鼠随机分为研究组和对照组，每组10只，应用改良的自由落体方法制备脑损伤模型，伤后1 d研究组大鼠脑实质内移植胚胎神经干细胞，对照组大鼠注射等量不含干细胞的培养液。在脑损伤前1 d、伤后1 d、1周、2周运用神经学缺损评分法评价大鼠运动神经功能。移植后2周，取脑组织分别行苏木精-伊红染色、抗BrdU、胶质纤维酸性蛋白、β微管蛋白Ⅲ和酪氨酸羟化酶免疫组化染色。　　结果与结论：伤后1，2周研究组大鼠的神经学缺损评分均显著低于对照组(P <0.05)。研究组大鼠受损脑组织中有较多的BrdU阳性神经干细胞，一部分细胞呈胶质纤维酸性蛋白、β微管蛋白Ⅲ和酪氨酸羟化酶阳性表达，对照组大鼠受损脑组织中未见有BrdU阳性细胞。实验结果表明，立体定向脑内移植神经干细胞可以在颅脑损伤灶中增殖分化，进而显著改善大鼠的神经运动功能。%BACKGROUND:Cel replacement therapy as an effective strategy for reconstruction of the central nervous system has very broad application prospects. OBJECTIVE:To investigate the effect of stereotactic transplantation of neural stem cels into the brain on the neuromotor function of craniocerebral trauma rats. METHODS:Twenty male Sprague-Dawley rats were equivalently randomized into study and control groups. Animal models of craniocerebral trauma were made using the improved free-fal method in the rats. Then, model rats in the study and control groups were given parenchymal transplantation of embryonic neural stem cels and the same volume of culture medium with no stem cels at 1 day after injury, respectively. Neuromotor function of rats was assessed based on the neurological severity scores. At 2 weeks after transplantation, brain tissues were taken for hematoxylin-eosin staining, anti-BrdU, glial fibrilary acidic protein, β-tubulin III and tyrosine hydroxylase immunohistochemistry staining. RESULTS AND CONCLUSION:The neurological severity scores in the study group were significantly lower than those in the control group at 1 and 2 weeks after injury (P< 0.05). In the study group, there were many BrdU-positive neural stem cels in the brain tissues, some of which were positive for glial fibrilary acidic protein, β-tubulin III and tyrosine hydroxylase; while in the control group, there was no BrdU-positive cel in the brain tissues. Experimental findings show that neural stem cels stereotacticaly transplanted into the brain can proliferate and differentiate in the brain lesion, and thereby notably improve the neuromotor function of rats with craniocerebral trauma.