Bouldin T W, Earnhardt T S, Goines N D, Goodrum J
Department of Pathology, School of Medicine, The University of North Carolina, Chapel Hill 27599-7525.
Neurotoxicology. 1989 Spring;10(1):79-89.
The appearance of endoneurial edema early in the evolution of tellurium neuropathy raises the possibility that a breakdown of the blood-nerve barrier (BNB) plays a role in the pathogenesis of the tellurium-induced demyelination. To investigate this possibility, we correlated the temporal onset of breakdown of the BNB with inhibition of cholesterol synthesis and ultrastructural abnormalities in sciatic nerve of weanling Long-Evans rats fed a diet containing 1.1% elemental tellurium. Permeability of the BNB was assessed with [125I]-albumin and horseradish peroxidase (HRP); cholesterol synthesis was assessed by incubating segments of sciatic nerve in vitro with [1-14C]acetate. Cholesterol synthesis was severely inhibited and labeled squalene was accumulating in sciatic nerve at 12 hr of tellurium exposure. The permeability of the BNB progressively increased between 24 hr and 72 hr of tellurium exposure. Membrane-delimited vacuoles, lipid droplets and cytoplasmic excrescences appeared in myelinating Schwann cells at 24 hr; demyelinating axons appeared at 48 hr of tellurium exposure. These observations suggest that factors other than BNB breakdown and vasogenic endoneurial edema are responsible for the initial Schwann-cell injury in tellurium neuropathy. However, the early onset of BNB breakdown may have a synergistic role in the pathogenesis of tellurium-induced demyelination.
在碲中毒性神经病发展早期出现的神经内膜水肿提示，血神经屏障（BNB）的破坏可能在碲诱导的脱髓鞘发病机制中起作用。为了研究这种可能性，我们将断奶的Long-Evans大鼠喂食含1.1%元素碲的饲料后，坐骨神经中BNB破坏的时间与胆固醇合成抑制及超微结构异常进行了关联。用[125I] -白蛋白和辣根过氧化物酶（HRP）评估BNB的通透性；通过在体外将坐骨神经节段与[1-14C]醋酸盐孵育来评估胆固醇合成。在碲暴露12小时时，胆固醇合成受到严重抑制，标记的鲨烯在坐骨神经中蓄积。在碲暴露24小时至72小时之间，BNB的通透性逐渐增加。在24小时时，髓鞘形成的施万细胞中出现膜界定的空泡、脂滴和细胞质突起；在碲暴露48小时时出现脱髓鞘轴突。这些观察结果表明，除了BNB破坏和血管源性神经内膜水肿外，其他因素也参与了碲中毒性神经病中施万细胞的初始损伤。然而，BNB破坏的早期发生可能在碲诱导的脱髓鞘发病机制中起协同作用。
