Previous studies of acrylamide (ACR) neuropathy in rat PNS [Toxicol. Appl. Pharmacol. 151 (1998) 211] and cerebellum [NeuroToxicology 23 (2002) 397] have suggested that axon degeneration was not a primary effect and was, therefore, of unclear neurotoxicological significance. To continue morphological examination of ACR neurotoxicity in CNS, a cupric silver stain method was used to define spatiotemporal characteristics of nerve cell body, dendrite, axon and terminal degeneration in brainstem and spinal cord. Rats were exposed to ACR at a dose-rate of either 50 mg/kg per day (i.p.) or 21 mg/kg per day (p.o.), and at selected times brains and spinal cord were removed and processed for silver staining. Results show that intoxication at the higher ACR dose-rate produced a nearly pure terminalopathy in brainstem and spinal cord regions, i.e. widespread nerve terminal degeneration and swelling were present in the absence of significant argyrophilic changes in neuronal cell bodies, dendrites or axons. Exposure to the lower ACR dose-rate caused initial nerve terminal argyrophilia in selected brainstem and spinal cord regions. As intoxication continued, axon degeneration developed in white matter of these CNS areas. At both dose-rates, argyrophilic changes in brainstem nerve terminals developed prior to the onset of significant gait abnormalities. In contrast, during exposure to the lower ACR dose-rate the appearance of axon degeneration in either brainstem or spinal cord was relatively delayed with respect to changes in gait. Thus, regardless of dose-rate, ACR intoxication produced early, progressive nerve terminal degeneration. Axon degeneration occurred primarily during exposure to the lower ACR dose-rate and developed after the appearance of terminal degeneration and neurotoxicity. Spatiotemporal analysis suggested that degeneration began at the nerve terminal and then moved as a function of time in a somal direction along the corresponding axon. These data suggest that nerve terminals are a primary site of ACR action and that expression of axonopathy is restricted to subchronic dosing-rates.

中文翻译：

---

丙烯酰胺神经病。二。脑干和脊髓中神经细胞损伤的时空特征。

先前对大鼠PNS中丙烯酰胺（ACR）神经病的研究[毒理学杂志。应用 Pharmacol。151（1998）211]和小脑[NeuroToxicology 23（2002）397]提示轴突变性不是主要作用，因此尚不清楚神经毒理学的意义。为了继续进行中枢神经系统中ACR神经毒性的形态学检查，使用铜银染色法定义了脑干和脊髓中神经细胞体，树突，轴突和终末变性的时空特征。将大鼠以每天50 mg / kg（ip）或每天21 mg / kg（po）的剂量率暴露于ACR，然后在选定的时间取出大脑和脊髓并进行银染处理。结果表明，较高的ACR剂量下的中毒在脑干和脊髓区域产生了几乎纯的终末病，即 在神经元细胞体，树突或轴突没有明显的嗜银性改变的情况下，存在广泛的神经末梢变性和肿胀。暴露于较低的ACR剂量率会在选定的脑干和脊髓区域引起最初的神经末梢嗜银粒细胞增多。随着中毒的继续，这些中枢神经系统区域的白质中出现了轴突变性。在两种剂量率下，脑干神经末梢的嗜银性变化均在明显的步态异常发作之前发生。相反，在暴露于较低的ACR剂量率期间，就步态变化而言，脑干或脊髓中轴突变性的出现相对延迟。因此，无论剂量率如何，ACR中毒都会导致早期进行性神经末梢变性。轴突变性主要发生在暴露于较低的ACR剂量率期间，并在出现终末变性和神经毒性后发展。时空分析表明，变性开始于神经末梢，然后随着时间的推移沿着相应的轴突沿躯体方向移动。这些数据表明神经末梢是ACR作用的主要部位，轴突病变的表达仅限于亚慢性剂量。