Descriptive morphology of developing fetal neostriatal allografts in the rhesus monkey: A correlated light and electron microscopic golgi study

Abstract

Primate fetal striatal neurons were transplanted into the ibotenic acid lesioned rhesus monkey striatum. Ten weeks after transplantation the monkeys were transcardially perfused and graft tissue was histologically stained, Golgi impregnated, and processed for electron microscopy. The monkeys received magnetic resonance imaging (MRI) scans before lesioning, after lesioning, and ten weeks after transplantation to noninvasively study the striatal grafts. The study demonstrated that fetal striatal grafts, measuring up to 0.4 × 0.8 cm, can survive for extended periods of time in the non-human primate. Hematoxylin-eosin stained sections of the transplant demonstrated that neuronal, glial, vascular, and lymphocytic cells were present in the graft. The majority of the neurons had somatic diameters between 8 and 20 μm and were characterized by nuclei containing multiple nucleoli. A few neurons within the graft had somatic diameters up to 40 μm. These larger neurons exhibited more mature cytoplasm containing a moderate amount of Nissl substance. Some of the blood vessels within the graft were surrounded by a large number of plasma cells, but there was no evidence of hemorrhage or necrosis. Bielschowsky staining and Golgi impregnation of the transplanted tissue demonstrated that there were neurons at various degrees of differentiation. Some of the neurons had varicose dendrites, growth cones, and filopodia, which are all characteristics of immature neurons, while others had a much more mature appearance, including a moderate number of dendritic spines. Some of these neurons had an appearancetypical of differentiating “medium spiny” neurons of the normal striatum. Electron microscopic analysis of the transplanted tissue and individual Golgi-impregnated neurons within the transplant confirmed that there were developing neurons within the graft. These neurons had an increased nuclear-to-cytoplasmic ratio and had nuclei containing multiple nucleoli. The neuropil surrounding these neurons was loosely organized and contained large areas of extracellular space. The neuropil exhibited developing dendrites, numerous growth cones, and mature synapses. In summary, the study demonstrated that fetal striatal allografts can survive for up to three months in the rhesus monkey and undergo normal differentiation as assessed by Golgi impregnation and electron microscopy.