Hausmann B, Sievers J, Hermanns J, Berry M
Department of Anatomy, University of Kiel, Kiel, Federal Republic of Germany.
J Comp Neurol. 1989 Mar 15;281(3):447-66. doi: 10.1002/cne.902810309.
After transection of the optic nerve of adult rats, most of the axons in the proximal stump die and the surviving ones are unable to regenerate into the distal optic nerve. Since the fetal brain has an inherent capacity to regenerate axons, we investigated whether fetal (E16) target regions of optic axons (thalamus and tectum) transplanted to the completely transected optic nerve of adult rats would promote axon regeneration. In control operated rats, axon growth beyond the site of transection was restricted to a few fibers that grew irregularly within the connective tissue scar. By contrast, in grafted animals directed outgrowth of optic axons toward the transplant started at 6 days postoperation (p.o.) and reached its maximum 15 days p.o. and later, when numerous single optic fibers and small axon fascicles had grown toward and into the graft, where they formed arborizations and terminal varicosities. Regenerating optic axons were further advanced than GFAP-positive strands of astroglia that emanated from the proximal optic nerve stump. Laminin immunoreactivity appeared at 6 days p.o. in the zone of reactive astroglia in the terminal part of the optic nerve stump. Later it showed a distribution complementary to the pattern of GFAP immunoreactivity, which it seemd to circumscribe. There was no unequivocal codistribution of laminin immunoreactivity with regenerating axons. In further experiments, target regions from different ontogenetic stages (E14 to neonate and adult) and nontarget regions (E16, cerebral cortex or spinal cord) were grafted to the optic nerve stump. With the exception of the adult grafts, all transplants had effects on axon regeneration comparable to those of E16 target regions. In order to test the effects of extracellular matrix molecules on axon regeneration, a basement membrane gel reconstituted from individual components of the Engelbreth-Holm-Sarcoma (EHS) sarcoma was implanted between proximal and distal optic nerve stumps. No axons were induced to regenerate by this matrix. Likewise, laminin adsorbed to nitrocellulose paper and implanted at the lesion site did not stimulate axon growth from the proximal optic nerve stump. These results indicate that fetal brain is able to induce and direct regrowth of axons from the optic nerve toward the graft across a substrate that is not composed of astroglia or basement membrane components like laminin. The directed growth of axons in the absence of a preformed substrate implies a chemotactic growth response along a concentration gradient mediated by neurotropic molecules released from the graft.
成年大鼠视神经横断后，近端残端的大多数轴突死亡，存活的轴突无法再生进入远端视神经。由于胎儿脑具有轴突再生的内在能力，我们研究了将视神经（丘脑和顶盖）的胎儿（E16）靶区移植到成年大鼠完全横断的视神经是否会促进轴突再生。在对照手术的大鼠中，轴突生长超出横断部位仅限于少数在结缔组织瘢痕内不规则生长的纤维。相比之下，在移植动物中，视神经轴突向移植部位的定向生长在术后6天开始，术后15天及之后达到最大值，此时大量单根视神经纤维和小的轴突束向移植部位生长并进入其中，在那里形成分支和终末膨体。再生的视神经轴突比从近端视神经残端发出的GFAP阳性星形胶质细胞链更向前延伸。层粘连蛋白免疫反应性在术后6天出现在视神经残端末端的反应性星形胶质细胞区域。后来它显示出与GFAP免疫反应性模式互补的分布，似乎围绕着GFAP。层粘连蛋白免疫反应性与再生轴突没有明确的共分布。在进一步的实验中，将来自不同个体发育阶段（E14至新生儿和成年）的靶区和非靶区（E16、大脑皮层或脊髓）移植到视神经残端。除成年移植外，所有移植对轴突再生的影响与E16靶区相当。为了测试细胞外基质分子对轴突再生的影响，将由恩格尔布雷特 - 霍尔姆 - 萨尔科马（EHS）肉瘤的单个成分重构的基底膜凝胶植入近端和远端视神经残端之间。这种基质没有诱导轴突再生。同样，吸附在硝酸纤维素纸上并植入损伤部位的层粘连蛋白也没有刺激近端视神经残端的轴突生长。这些结果表明，胎儿脑能够诱导并引导视神经轴突跨越不是由星形胶质细胞或层粘连蛋白等基底膜成分组成的基质向移植部位再生。在没有预先形成的基质的情况下轴突的定向生长意味着沿着由移植释放的神经营养分子介导的浓度梯度的趋化生长反应。
