Hudson J L, Hoffman A, Strömberg I, Hoffer B J, Moorhead J W
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Neurosci Lett. 1994 Apr 25;171(1-2):32-6. doi: 10.1016/0304-3940(94)90597-5.
Fetal central nervous system transplants to the adult brain have been utilized to understand brain connectivity and as replacement therapy in Parkinson's disease (PD). Here we use fetal brain allografting in the rat unilaterally depleted of dopamine, a unilateral model of PD, and apomorphine-induced rotations as an index of graft functional status while peripherally manipulating the host's alloimmune status. This system allows the investigator to examine, dynamically, host-allograft interactions in the brain under differing states of alloimmunoreactivity without the need to biopsy or sacrifice the animal. In addition to this novel application, we established that brain allografts are differentially susceptible to immunologic attack depending upon the graft's duration of residence in the host brain. Increasing residence time increases graft 'rejectability' to peripheral allosensitization. Passive immunization also sensitizes the host to subsequent graft rejection. Lastly, simple host alloimmunocompetence is necessary but not sufficient to cause fetal graft 'rejection', defined as a return of apomorphine-induced rotations.
将胎儿中枢神经系统移植到成年大脑中，已被用于了解大脑的连接性，并作为帕金森病（PD）的替代疗法。在这里，我们在单侧多巴胺耗尽的大鼠中使用胎儿脑同种异体移植，这是一种PD的单侧模型，并将阿扑吗啡诱导的旋转作为移植物功能状态的指标，同时对外周宿主的同种免疫状态进行操作。该系统使研究人员能够动态地检查在不同同种免疫反应状态下大脑中宿主与移植物之间的相互作用，而无需对动物进行活检或处死。除了这种新应用外，我们还确定脑同种异体移植物对免疫攻击的易感性因移植物在宿主脑中的停留时间而异。停留时间的增加会增加移植物对外周同种致敏的“可排斥性”。被动免疫也会使宿主对随后的移植物排斥敏感。最后，单纯的宿主同种免疫能力是导致胎儿移植物“排斥”（定义为阿扑吗啡诱导的旋转恢复）的必要条件，但不是充分条件。
