BRAIN TRANSPLANTS IN GENETIC ANALYSIS

实验性变态反应性脑脊髓炎(EAE)是一种自身免疫器官 易感动物接种沙门氏菌引起的特殊疾病 佐剂中的中枢神经系统(CNS)抗原。EAE的特征是 病理上由炎症和脱髓鞘引起的。易感性是 基因决定的。先前的研究表明，基因限制是 不限于免疫系统，并暗示限制因素在 抗原源和中枢神经系统的水平。建议的研究是设计的 为了确定抗原源、宿主免疫系统所起的作用 以及靶向中枢神经系统在疾病发生发展中的作用。这将会实现的 通过在EAE之间使用相互的异位脑移植 易感和耐药的小鼠。胎儿脑组织的移植将是 放入眼睛的前房，并让其在 疾病诱导。将监测动物的EAE临床症状和 本地人炎症和脱髓鞘的组织病理学发展 中枢神经系统和移植组织。血脑屏障的完整性 (Bbb)，一个潜在的中枢神经系统限制的地点，也将在 天然中枢神经系统和移植组织对其通透性的评价 未接种时对台盼蓝染料和辣根过氧化物酶的影响 在引发疾病之后。这些学习，通过就业 移植技术，将允许表型特征的 以一种以前不可能的方式进行遗传限制的地点(S)；分离 宿主免疫能力在由此引发的疾病发展中的作用 抗原源和目标中枢神经系统的关系。这样的信息不仅 为这种疾病的发病机制提供了洞察力，但也表明 预防或治疗中潜在的治疗性干预部位 这样的疾病。

Experimental allergic encephalomyelitis (EAE) is an autoimmune, organ specific disorder produced by inoculation of susceptible animals with central nervous system (CNS) antigens in adjuvants. EAE is characterized pathologically by inflammation and demyelination. Susceptibility is genetically determined. Previous studies indicate genetic restriction is not limited to the immune system and suggest restrictive elements at the level of the antigen source and the CNS. The proposed studies are designed to identify the role played by the antigen source, the host immune system and the target CNS in the development of disease. This will be achieved through the use of reciprocal heterotopic brain transplants between EAE susceptible and resistant mice. Transplants of fetal brain tissue will be placed into the anterior chamber of the eye and allowed to mature before disease induction. Animals will be monitored for clinical signs of EAE and histopathologic development of inflammation and demyelination in the native CNS and the transplanted tissues. The integrity of the blood-brain barrier (BBB), a potential site of CNS restriction, will also be evaluated in the native CNS and transplanted tissues by assessing permeability of their vessels to trypan blue dye and horseradish peroxidase when uninoculated and following the induction of disease. These studies, through the employment of transplant technology, will allow phenotypic characterization of the site(s) of genetic restriction in a way not previously possible; separating the role of host immune competence in the development of disease from that of the antigen source and the target CNS. Such information not only provides insight into the pathogenesis of this disease, but also indicates potential sites for therapeutic intervention in the prevention or treatment of such disease.