Cece R, Petruccioli M G, Pizzini G, Cavaletti G, Tredici G
Institute of Normal Human Anatomy, University of Milan, Italy.
J Submicrosc Cytol Pathol. 1995 Oct;27(4):417-25.
Different substances may induce neurological impairment, clinically expressed as peripheral neuropathies, due to damage of the neuronal bodies (neuronopathy) of sensory or motor neurons. Neuronopathies have generally been studied referring to neurons, although other cellular components may also be damaged. Cisplatin (CDDP) is known to be neurotoxic to the neurons of the dorsal root ganglia (DRG). The scarcity of information as to the possible involvement and role played by dorsal root ganglion (DRG) satellite cells in neuronopathies prompted this study using the chronic DRG neuronopathy induced by the repeated administration of CDDP in rats as a model. Eighteen female Wistar rats were treated according to 3 different schedules of CDDP administration (6 rats for each group). Six further animals were used as controls. At the end of the experiment the L4-L5-L6 dorsal root ganglia were examined at the light and electron microscope. Ag-NOR reaction was also examined in 4 further CDDP-treated rats and 4 controls. Pathological changes in satellite cells of animals treated with CDDP were remarkable in the nucleus where heterochromatin clumps were reduced or even completely absent. Morphometric analysis of the area occupied by heterochromatin indicated that this nuclear component decreased in an exposure-time dependent manner. Frequently, nucleolar-like structures became apparent in the nucleus of the rats treated with the higher doses of CDDP. Ag-NOR positive regions in the nuclei of treated rats were increased with respect to the controls. Cytoplasmic changes in DRG satellite cells of CDDP treated rats were limited, being characterized by an increased electron-density of the matrix. In treated rats deep invaginations between satellite cells and the neuronal surface were evident, leading to the formation of vacuoli. The interstitial connective space often showed edematous areas. Our observations demonstrate that in chronic cisplatin neuronopathy, DRG satellite cells are also involved in the pathological changes induced by drug exposure, and that these changes may be interpreted as being mainly reactive.
不同物质可能会导致神经损伤，临床上表现为周围神经病变，这是由于感觉或运动神经元的神经元体（神经元病）受损所致。尽管其他细胞成分也可能受损，但神经元病通常是针对神经元进行研究的。顺铂（CDDP）已知对背根神经节（DRG）的神经元具有神经毒性。关于背根神经节（DRG）卫星细胞在神经元病中可能的参与情况和作用的信息匮乏，促使本研究以大鼠反复给予CDDP诱导的慢性DRG神经元病为模型。18只雌性Wistar大鼠按照3种不同的CDDP给药方案进行治疗（每组6只大鼠）。另外6只动物用作对照。实验结束时，对L4-L5-L6背根神经节进行光镜和电镜检查。还对另外4只经CDDP处理的大鼠和4只对照进行了Ag-NOR反应检查。用CDDP处理的动物卫星细胞的病理变化在细胞核中很明显，其中异染色质团块减少甚至完全消失。对异染色质所占面积的形态计量分析表明，这种核成分以暴露时间依赖的方式减少。在用高剂量CDDP处理的大鼠细胞核中，经常会出现核仁样结构。与对照相比，经处理大鼠细胞核中的Ag-NOR阳性区域增加。CDDP处理大鼠的DRG卫星细胞的细胞质变化有限，其特征是基质的电子密度增加。在处理的大鼠中，卫星细胞与神经元表面之间的深凹陷很明显，导致形成空泡。间质结缔组织间隙经常出现水肿区域。我们的观察结果表明，在慢性顺铂神经元病中，DRG卫星细胞也参与了药物暴露引起的病理变化，并且这些变化可能主要被解释为反应性的。
