Giacobini M M, Olson L, Hoffer B J, Sara V R
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Exp Neurol. 1990 Apr;108(1):33-7. doi: 10.1016/0014-4886(90)90004-c.
Truncated IGF-1 (tIGF-1), a form of IGF-1 identified in the human brain, has been suggested, from in vitro experiments, to exert neurotrophic effects on developing fetal brain tissue. We studied the effects of tIGF-1 and IGF-1 on small defined areas of the developing central nervous system by using the in vivo model of intraocular transplantation which allows for direct observations of graft survival and growth. Truncated IGF-1 was found to significantly enhance the growth of fetal spinal cord (Embryonic Day (E) 14) and parietal cortex (E16-17) grafts transplanted to the anterior chamber of the eye of adult rats. tIGF-1 increased the volume of cerebral cortex grafts by approximately 100% and of E14 spinal cord grafts by approximately 50%. E18 spinal cord grafts and hippocampal grafts were not stimulated by tIGF-1 as compared to controls given HSA. Effects in cortex were seen with tIGF-1 using concentrations down to at least 10 ng/microliters. Interestingly, intact IGF-1 had no effect on cortical grafts. These findings show for the first time, using an in vivo system, that tIGF-1 is a potent stimulator of growth of grafted fetal cortex cerebri and spinal cord and suggest a possible role for endogenous tIGF-1 in cortical and spinal cord development.
截短型胰岛素样生长因子-1(tIGF-1)是在人类大脑中发现的一种胰岛素样生长因子-1形式,体外实验表明,它对发育中的胎儿脑组织具有神经营养作用。我们通过眼内移植的体内模型,研究了tIGF-1和胰岛素样生长因子-1(IGF-1)对发育中的中枢神经系统特定小区域的影响,该模型能够直接观察移植物的存活和生长情况。结果发现,截短型胰岛素样生长因子-1能显著促进移植到成年大鼠眼前房的胎儿脊髓(胚胎第14天)和顶叶皮质(胚胎第16 - 17天)移植物的生长。tIGF-1使大脑皮质移植物的体积增加了约100%,使胚胎第14天的脊髓移植物体积增加了约50%。与给予人血清白蛋白(HSA)的对照组相比,tIGF-1对胚胎第18天的脊髓移植物和海马体移植物没有刺激作用。使用低至至少10纳克/微升的浓度时,tIGF-1对皮质移植物有作用。有趣的是,完整的IGF-1对皮质移植物没有影响。这些发现首次使用体内系统表明,tIGF-1是移植的胎儿大脑皮质和脊髓生长的有效刺激因子,并提示内源性tIGF-1在皮质和脊髓发育中可能发挥作用。