BRAIN TRANSPLANTS IN GENETIC ANALYSIS

实验性变态反应性脑脊髓炎（EAE）是一种自身免疫性， 通过接种易感动物而产生的特定疾病 佐剂中的中枢神经系统（CNS）抗原。 EAE的特点是 病理上是炎症和脱髓鞘。 易感性 基因决定的。 以前的研究表明，遗传限制是 不限于免疫系统，并建议限制性因素， 抗原来源和中枢神经系统的水平。 拟议的研究旨在 为了确定抗原来源、宿主免疫系统所起的作用， 以及疾病发展过程中的目标中枢神经系统。 完成这项工作的方法是 通过在EAE之间使用相互异位脑移植， 易感和耐药小鼠。 胎儿脑组织的移植 放入眼前房中， 疾病诱导 将监测动物的EAE临床体征， 炎症和脱髓鞘的组织病理学发展， CNS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位点，也将在 天然CNS和移植组织通过评估其渗透性， 当未接种时，将容器置于台盼蓝染料和辣根过氧化物酶中， 在诱发疾病之后。 这些研究，通过就业 移植技术，将允许表型表征的 以以前不可能的方式进行遗传限制的位点;分离 宿主免疫能力在疾病发展中的作用， 抗原源和靶中枢神经系统。 这些信息不仅 提供了深入了解这种疾病的发病机制，但也表明， 在预防或治疗中进行治疗干预的潜在部位 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.