Sarnat H B, Nochlin D, Born D E
Department of Neurology, University of Washington School of Medicine, Seattle 98195, USA.
Brain Dev. 1998 Mar;20(2):88-94. doi: 10.1016/s0387-7604(97)00111-3.
Neuronal nuclear antigen (NeuN) immunocytochemistry was studied in 15 normal human fetal nervous systems of 8-24 weeks gestation and in four term neonates. Material was derived from products of conception or from autopsy. Antigen retrieval was enhanced for immunocytochemistry by microwave heating of formalin-fixed paraffin sections. NeuN appears highly specific as a marker of neuronal nuclei in human fetal brain. Only rare nuclei are recognized in the germinal matrix. Cerebellar external granule cells are more strongly immunoreactive than postmigratory internal granule cells until 24 weeks gestation; by term most internal and only a few external granule cells are recognized by NeuN antibody. In the cerebrum, some reactive nuclei are demonstrated along radial glial fibers, particularly near the cortical plate. Within the cortical plate, only deep neurons (future layers 4-6) are marked at 19-22 weeks, but by 24 weeks most neurons in the cortical plate exhibit immunoreactivity, though at term some in layer 2 are still non-reactive. Some neurons fail to be recognized by NeuN at all ages: Cajal-Retzius cells, Purkinje cells, inferior olivary and dentate nucleus neurons, and sympathetic ganglion cells are examples. Despite their common origin in the cerebellar tubercle, basal pontine neurons are strongly reactive even before midgestation, hence NeuN does not predict embryonic origin. Neurons of dorsal root and cranial nerve ganglia are reactive even at 8 weeks. This study of normal fetal central nervous system provides a basis for neuropathological evaluation and as a prelude to applications in cerebral dysgeneses.
在15例妊娠8 - 24周的正常人类胎儿神经系统以及4例足月儿的神经系统中，研究了神经元核抗原（NeuN）免疫细胞化学。材料取自流产产物或尸检样本。通过对福尔马林固定石蜡切片进行微波加热，增强了免疫细胞化学的抗原修复。NeuN作为人类胎儿脑神经元核的标志物具有高度特异性。生发基质中仅见极少数细胞核被识别。直到妊娠24周，小脑外颗粒细胞的免疫反应性比迁移后的内颗粒细胞更强；足月时，NeuN抗体仅识别大多数内颗粒细胞和少数外颗粒细胞。在大脑中，沿放射状胶质纤维可见一些反应性细胞核，尤其是在皮质板附近。在皮质板内，仅在19 - 22周时深层神经元（未来的第4 - 6层）有标记，但到24周时皮质板中的大多数神经元呈现免疫反应性，不过足月时第2层的一些神经元仍无反应。有些神经元在所有年龄段均未被NeuN识别：例如 Cajal - Retzius细胞、浦肯野细胞、下橄榄核和齿状核神经元以及交感神经节细胞。尽管脑桥基底部神经元共同起源于小脑结节，但即使在妊娠中期之前它们就具有强烈的反应性，因此NeuN不能预测胚胎起源。背根神经节和脑神经节的神经元在8周时就有反应。这项对正常胎儿中枢神经系统的研究为神经病理学评估提供了基础，并为脑发育异常的应用研究奠定了基础。
