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

实验性中枢神经系统畸形的胚胎发病机制及胎间神经移植的功能恢复

基本信息

批准号：
01570812
负责人：
OI Shizuo
金额：
$ 1.41万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

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

脊柱裂患者的截瘫状态（脊髓劈裂），其是先天性脊髓旁疾病的最常见原因，在患者的整个生命中仍然存在。手术适应症和治疗方式一直存在争议，现在越来越明显的是，有两个矛盾的治疗目标可供选择，在产前诊断或根治性手术干预下终止妊娠，以重建神经结构。20世纪80年代初，两位作者报道了神经吻合术在脊柱裂患者中的临床应用（Epstein F.等和Oi，S.等人），即“肋间神经至腰神经根吻合术”。基于这些历史背景，作者在临床实例和实验模型中研究了书写障碍状态下神经元的成熟过程。结果揭示了一个事实， ...更多信息神经元的发育不是单调地受到抑制，而是部分地过度成熟。过成熟神经元成分中含有生长抑素阳性成分，提示神经元过成熟或某些神经肽发育错误的方向。这些神经元的无序发育在头神经管闭锁中广泛存在，而在脊髓管闭锁中神经基板是这些过度生长的神经元生长的焦点。还打算采用全胚胎培养技术制作维生素A诱导的大鼠脊柱裂新实验模型，并从形态学角度探讨其胚胎发病机制。此外，在该模型中，进行胎鼠脊髓移植以修复脊髓神经功能的先天性缺损。从这些研究中所获得的知识，强调神经重建程序应进行的过程中，神经元的成熟，即。e.在胎儿时期，为了发展适当的神经网络和神经连接。少