Embryopathogenesis of experimental CNS malformations and functional recovery by fetus to fetus neurostransplantation

摘要脊柱裂（髓裂）患者的截瘫状态是导致先天性截瘫最常见的原因，其截瘫状态会伴随患者的一生，手术适应证和治疗方式一直存在争议，目前越来越明显地存在两种相互矛盾的治疗目标选择，即在产前诊断下终止妊娠或根治性手术干预重建神经结构。20世纪80年代初，Epstein F. et al和Oi， S. et al两位作者报道了神经吻合术在脊柱裂患者中的临床应用，即“肋间神经-腰神经根吻合术”。结果并不令人满意，无法获得功能恢复。基于这些历史背景，作者通过临床实例和实验模型研究了异常状态下的神经元成熟过程。结果揭示了一个事实，即更多的神经元发育不是单调地受到抑制，而是部分过度成熟。过度成熟的神经元成分包括生长抑素，这一阳性成分提示了某些神经肽的神经过度成熟或发育错误的方向。这些无序发育的神经元在头侧发育障碍中被广泛发现，而在脊柱发育障碍中，神经基质是生长过度的神经元的焦点。采用全胚培养技术，建立了维生素a诱导的大鼠脊柱裂实验模型，并从形态学角度对其胚胎发生进行了研究。在此基础上，采用胎儿间脊髓移植修复先天性脊髓神经功能缺损。从这些研究中获得的知识，强调神经重建手术应在神经元成熟的过程中进行，即在胎儿时期，以发展适当的神经网络和神经连接。少

AbstractThe paraplegic status in patient with spina bifida(myeloschisis), which is the most common cause for congential paraparetic condition, remains for the entire life of the patient The operative indications and therapeutic modalities have been controversial and it is now becoming more apparent that there are two contradictory therapeutic goals to be selected, termination of the pregnancy under the prenatal diagnosis or radical surgical intervention to reconstruct the neural structures. In early 1980s, clinical application of nerve anastomosis in patients with spina bifida was reported by two authors(Epstein F. et al and Oi, S. et al), namely "Intercostal Nerve to lumbar Nerve Root Anastomosis". The results were not satisfactory enough to obtain the functional recovery.Based on these historical backgrounds, the authors have investigated the neuronal maturation process in dysraphic states both in the clinical examples and the experimental models. The results disclosed a fact that th … More e neuronal developments were not monotonously suppressed but partly overmatured. The overmatured neuronal components included somatostatin - positive element suggesting the direction of the neuronal overmaturation or developmental error- of certain neuropeptide. These disorderly developed neurons were diffusely identified in cephalic -dysraphysm, while the neural placode was the focus to grow such overgrown neurons in spinal dysraphism. By using a whole-embryo culture technique, a new experimental rat spina bifida model induced by vitamin A was also intended to be made, and its embryopathogenesis was investigated from a viewpoint of morphology. Furthermore, a fetus to fetus spinal cord transplantation was performed to repair the congenital gap of the spinal cord neural function in this model. From the knowledge obtained in these studies, it was emphasized that the neural reconstructive procedure should be undertaken on the process of neuronal maturation, i. e. during the fetal period, in order to develop the proper neural networks and neural connections. Less