Nerve growth factor intervention triggers changes in the neural stem cells of experimental autoimmune encephalomyelitis rats

doi:10.3969/j.issn.2095-4344.2016.45.021

Abstract

Abstract:

BACKGROUND: Nerve growth factor is a neurotrophic factor that is involved in the cell regulation and promotes the proliferation of neural stem cells.
OBJECTIVE: To observe the effect of nerve growth factor on neural stem cells of experimental autoimmune encephalomyelitis rats.
METHODS: Wistar rats, 3 weeks of age, were randomly divided into control group, encephalomyelitis model group, nerve growth factor treatment group. Rat models of experimental autoimmune encephalomyelitis were made in the latter two groups. On the day of onset, rats in the nerve growth factor treatment group were given intraperitoneal injection of 1 000 U/kg nerve growth factor for 7 continuous days, and rats in the other two groups given no treatment. Effects of nerve growth factor on clinical symptoms of model rats were observed. Expression of Brdu in the subependymal zone and Brdu⁺/GFAP⁺ expression in the cortex were detected.
RESULTS AND CONCLUSION: Rat models of experimental autoimmune encephalomyelitis appeared to have encephalomyelitis symptoms successively at the beginning of 10-day immunization, while rats in the control group had no symptoms of encephalomyelitis. In the model group, glial cell hyperplasia, inflammatory cell infiltration, damage to vascular endothelial cell proliferation, and perivascular aggregation of inflammatory cells in the rat brain were found, while no abnormal changes in the rat brain were found in the control group. Compared with the model group, the expression of Brdu in the subependymal zone and Brdu⁺/GFAP⁺ expression in the cortex were both higher in the model group (P < 0.05), and these expressions were also higher in the nerve growth factor treatment group than the model group at 7 and 21 days after onset (P < 0.05). To conclude, these findings suggest that the rat model of autoimmune encephalomyelitis can be successfully established, and nerve growth factor treatment can improve clinical symptoms of experimental autoimmune encephalomyelitis rats by promoting the proliferation and differentiation of neural stem cells into astrocytes.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Stem Cells, Neural Stem Cells, Nerve Growth Factor, Encephalomyelitis, Tissue Engineering

CLC Number:

R394.2

Wang Xue-jun, Li Mao. Nerve growth factor intervention triggers changes in the neural stem cells of experimental autoimmune encephalomyelitis rats[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(45): 6827-6833.

Figures/Tables 1

2.1 实验动物数量分析纳入Wistar幼鼠42只，随机分为3组，全部进入结果分析，无脱失。 2.2 实验性自身免疫性脑脊髓炎幼鼠模型的建立和鉴定行为学改变：实验性自身免疫性脑脊髓炎幼鼠在免疫后出现食欲减退，体质量下降，在免疫后10 d出现第1例发病，随后幼鼠陆续发病，发病时间集中在免疫后12-13 d，发病的表现一般为先出现活动不灵活，步态笨拙，症状不断加重，最后出现后肢瘫痪。对照组大鼠体质量随着生长不断增加，观察1个月没有出现脑脊髓炎症状。苏木精-伊红染色结果：实验性自身免疫性脑脊髓炎幼鼠的脑组织中胶质细胞增生，出现炎症细胞浸润，血管内皮细胞增生破坏，炎症细胞呈“袖套”状集中在血管周围(见图1)。对照组的脑组织表现正常。 2.3 神经生长因子对实验性自身免疫性脑脊髓炎幼鼠临床症状的影响在神经生长因子治疗后第21天时对脑脊髓炎模型组幼鼠和脑脊髓炎神经生长因子治疗组幼鼠的临床症状进行比较，发现脑脊髓炎神经生长因子治疗组幼鼠的症状持续时间明显低于脑脊髓炎模型组(P < 0.05)，脑脊髓炎神经生长因子治疗组幼鼠的平均神经功能评分明显低于脑脊髓炎模型组(P < 0.05)，见表1。表明神经生长因子治疗能够改善实验性自身免疫性脑脊髓炎幼鼠的临床症状。 2.4 脑脊髓炎模型组和对照组幼鼠室管膜下区神经干细胞标记物Brdu表达情况比较由表2看出，脑脊髓炎模型组幼鼠的室管膜下区Brdu的表达均高于对照组(P < 0.05)，其中以脑脊髓炎发病后3 d组幼鼠的室管膜下区Brdu的表达最高，明显高于脑脊髓炎发病7 d组、脑脊髓炎发病21 d组和对照组(P < 0.05)。 2.5 脑脊髓炎模型组和脑脊髓炎神经生长因子治疗组幼鼠室管膜下区神经干细胞标记物Brdu表达情况比较由表3看出，脑脊髓炎神经生长因子治疗组幼鼠脑脊髓炎发病7 d和21 d组时室管膜下区Brdu的表达均显著高于脑脊髓炎模型组，差异有显著性意义(P < 0.05)，其中脑脊髓炎神经生长因子治疗组幼鼠以脑脊髓炎发病后7 d组的室管膜下区Brdu表达最高，显著高于脑脊髓炎发病3 d组和21 d组(P < 0.05)。 2.6 脑脊髓炎模型组和对照组幼鼠皮质区Brdu+/GFAP+表达情况比较由表4看出，脑脊髓炎模型组幼鼠的皮质区Brdu+/GFAP+表达高于对照组(P < 0.05)，其中以脑脊髓炎发病后3 d组幼鼠的皮质区Brdu+/GFAP+表达最高，明显高于脑脊髓炎发病21 d组和对照组(P < 0.05)。 2.7 脑脊髓炎模型组和脑脊髓炎神经生长因子治疗组幼鼠皮质区Brdu+/GFAP+表达情况比较由表5看出，脑脊髓炎神经生长因子治疗组幼鼠脑脊髓炎发病7 d组和21 d组的皮质区Brdu+/GFAP+表达均显著高于脑脊髓炎模型组(P < 0.05)，其中脑脊髓炎神经生长因子治疗组幼鼠以脑脊髓炎发病后7 d组的皮质区Brdu+/GFAP+表达最高，显著高于脑脊髓炎发病3 d组和21 d组(P < 0.05)。"

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