ALLOGENEIC GRAFTS OF FETAL DOPAMINE NEURONS - BEHAVIORAL INDEXES OF IMMUNOLOGICAL INTERACTIONS
ALLOGENEIC GRAFTS OF FETAL DOPAMINE NEURONS - BEHAVIORAL INDEXES OF IMMUNOLOGICAL INTERACTIONS
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DOI：
10.1016/0304-3940(94)90597-5
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发表时间：
1994-04-25
影响因子：
2.5
通讯作者：
MOORHEAD, JW
中科院分区：
文献类型：
--
作者：
HUDSON, JL;HOFFMAN, A;MOORHEAD, JW
胎儿中枢神经系统移植到成人大脑已被用于了解脑连接和作为帕金森病(PD)的替代疗法。在这里，我们使用单侧多巴胺耗竭的大鼠胎脑移植，这是一种单侧PD模型，并使用阿朴吗啡诱导的旋转作为移植功能状态的指标，同时外围操纵宿主的同种异体免疫状态。该系统允许研究人员在不同的同种免疫反应状态下动态检查大脑中宿主-同种异体移植物的相互作用，而不需要对动物进行活组织检查或牺牲。除了这一新的应用，我们建立了脑移植对免疫攻击的不同易感性，这取决于移植物在宿主大脑中的停留时间。延长停留时间会增加移植物对外周同种异体致敏的排斥反应。被动免疫也使宿主对随后的移植物排斥反应敏感。最后，简单的宿主同种异体免疫能力是必要的，但不足以导致胎儿移植物的‘排斥’，即阿朴吗啡诱导的旋转的恢复。
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.