Schwarz S C, Schwarz J, Sautter J, Oertel W H
Klinikum Grosshadern, Department of Neurology, LMU Munich, Germany.
Exp Brain Res. 1998 May;120(1):95-103. doi: 10.1007/s002210050381.
Activated microglia play an important role in the rejection of intracerebral grafts and the degeneration of axotomized neurones. We studied the effect of macrophage migration stimulatory factor (MSF) or macrophage migration inhibitory factor (MIF) on allogeneic foetal mesencephalic dopaminergic grafts transplanted into the striatum of 6-hydroxydopamine-lesioned rats. Rotation testing revealed a significant compensation of lesion-induced motor asymmetry 3 weeks post-grafting in animals treated with MIF and vehicle-treated controls compared with pre-graft values (Student's t-test, P < or = 0.005) and MSF-treated animals (ANOVA, post hoc Fisher PLSD test, P < or = 0.05). The MSF group showed no significant compensation. Graft recipients with MIF application (1452.06 +/- 164.32 tyrosine hydroxylase-positive ventral mesencephalic cells) and controls (1753.21 +/- 165.51 tyrosine hydroxylase-positive neurones) displayed good graft survival. Animals with MSF application showed a significant reduction of tyrosine hydroxylase-positive grafted cells (MSF 570.36 +/- 209.49 cells) and graft volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD test, P < or = 0.05). The proportional area of microglia was significantly reduced in MIF animals compared with control animals (ANOVA, post hoc Fisher PLSD test, P < or = 0.001). Activated microglia and macrophages were reduced by half in the MIF-treated group compared with MSF animals and controls. We conclude that intrastriatal injections of MSF result in impaired function and survival of allogeneic ventral mesencephalon (VM) grafts 3 weeks after transplantation. MIF can reduce the number of microglia and macrophages in allogeneic foetal VM grafts. A reduction of microglia via MIF application did not enhance graft function and survival.
活化的小胶质细胞在脑内移植排斥反应及轴突切断后神经元的变性过程中发挥重要作用。我们研究了巨噬细胞迁移刺激因子（MSF）或巨噬细胞迁移抑制因子（MIF）对移植到6-羟基多巴胺损伤大鼠纹状体内的同种异体胎儿中脑多巴胺能移植物的影响。旋转测试显示，与移植前值相比（学生t检验，P≤0.005）以及与MSF处理组动物相比（方差分析，事后费舍尔最小显著差异检验，P≤0.05），MIF处理组动物和赋形剂处理的对照组动物在移植后3周时，损伤诱导的运动不对称性得到了显著补偿。MSF组未显示出显著补偿。应用MIF的移植物接受者（1452.06±164.32个酪氨酸羟化酶阳性腹侧中脑细胞）和对照组（1753.21±165.51个酪氨酸羟化酶阳性神经元）显示移植物存活良好。与MIF组和对照组相比，应用MSF的动物酪氨酸羟化酶阳性移植细胞数量显著减少（MSF组为570.36±209.49个细胞），移植物体积也显著减小（方差分析，事后费舍尔最小显著差异检验，P≤0.05）。与对照动物相比，MIF处理组动物小胶质细胞的比例面积显著减小（方差分析，事后费舍尔最小显著差异检验，P≤0.001）。与MSF处理组动物和对照组相比，MIF处理组活化的小胶质细胞和巨噬细胞数量减少了一半。我们得出结论，纹状体内注射MSF会导致同种异体腹侧中脑（VM）移植物在移植后3周时功能受损且存活率降低。MIF可减少同种异体胎儿VM移植物中小胶质细胞和巨噬细胞的数量。通过应用MIF减少小胶质细胞数量并未增强移植物功能和存活率。
