Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic ''binge'' intoxication with ethanol: Possible explanation for olfactory deficits in alcoholics
Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic ''binge'' intoxication with ethanol: Possible explanation for olfactory deficits in alcoholics
复制标题
DOI：
10.1111/j.1530-0277.1996.tb01641.x
复制
发表时间：
1996-04-01
影响因子：
3.2
通讯作者：
Neafsey, EJ
中科院分区：
文献类型：
--
作者：
Collins, MA;Corso, TD;Neafsey, EJ
成年大鼠严重、重复（“狂饮”）乙醇中毒（根据 Majchrowicz 方法的修改，每天 3 次灌胃，持续 4 天）会导致与记忆和嗅觉相关的选定大脑皮层区域的神经元变性，证实了 Switzer 及其同事的结果（Anat Rec. 202: 186a, 1982）。使用 de Olmos 铜银技术对退化神经元和过程（嗜银症）进行可视化，并通过嗜银细胞/区域的总数和密度进行定量。退化的特异性为慢性酗酒者的嗅觉记忆缺陷提供了神经病理学基础。在高度中毒的大鼠中，嗜银症在海马齿状回颗粒细胞、内嗅皮层第三层锥体神经元和嗅球嗅神经末梢中最为广泛。退化的锥体神经元在岛叶皮质和嗅觉皮质区域（例如梨状皮质和鼻周围皮质）中也始终可见。海马 CA 区几乎没有嗜银神经元，小脑区也没有——在长期乙醇喂养模型中通常显示出细胞损失——但在 CA2 区观察到退化的杂乱纤维。在该模型中，在戒断症状高峰期之前，退化达到最大，因为与最后一次乙醇剂量后 8 小时相比，嗜银密度在 36 小时内没有增加。需要高血液乙醇水平，因为等热量对照中不存在嗜银症，并且仅在第 2 至 4 天平均血液乙醇水平高于 300 mg/dl 的乙醇中毒大鼠中才明显；然而，它在 350 至 550 mg/dl 之间大幅增加。嗜银分布与实验性癫痫发作中发生的区域神经病理学的相似性表明，乙醇诱导的变性可能具有兴奋性毒性基础。癫痫阈值的逐渐降低（例如，在暴饮乙醇中毒期间记录的点燃现象）可能与高血液和脑乙醇峰值之间重复最低点期间的兴奋性毒性过度活跃有关。然而，也可能涉及乙醇或其代谢物的直接毒性作用。总体而言，该模型对于研究乙醇引起的选择性皮质和嗅觉脑损伤的机制应该有用。
Severe, repetitive (''binge'') ethanol intoxication in adult rats (intragastric delivery 3 times daily for 4 days in a modification of the Majchrowicz method) precipitates neuronal degeneration in selected cerebral cortical regions involved in memory and olfaction, confirming the results of Switzer and colleagues (Anat Rec. 202: 186a, 1982). Neuronal damage was visualized with the de Olmos cupric silver technique for degenerating neurons and processes (argyrophilia), and was quantitated by total counts and densities of argyrophilic cells/fields, The specificity of the degeneration provides a neuropathological basis for the olfactory memory deficits in chronic alcoholics. In highly intoxicated rats, argyrophilia was most extensive among hippocampal dentate gyrus granule cells, pyramidal neurons in layer 3 of the entorhinal cortex, and olfactory nerve terminals in the olfactory bulb. Degenerating pyramidal neurons were also consistently seen in the insular cortex and olfactory cortical regions, such as the piriform and perirhinal cortices. There were few argyrophilic neurons in the CA regions of the hippocampus and none in the cerebellum-regions generally shown to have cell loss in long-term ethanol feeding models-but degenerating messy fibers in the CA2 region were observed. Degeneration was maximal before the peak period of abstinence symptoms in this model, because argyrophilic densities were no greater 36 hr, compared with 8 hr after the last ethanol dose. High blood ethanol levels were required, because argyrophilia, absent from isocaloric controls, also was only evident in ethanol-intoxicated rats with mean blood ethanol levels for days 2 to 4 above 300 mg/dl; however, it increased substantially between 350 and 550 mg/dl. The resemblance of the argyrophilic distribution to the regional neuropathology that occurs in experimental seizures indicates that the ethanol-induced degeneration may have an excitotoxic basis, Progressive reductions in the seizure threshold (e.g., kindling phenomena that have been documented during binge ethanol intoxication) might be associated with excito-toxic hyperactivity during the repetitive nadirs between high blood and brain ethanol peaks. However, direct toxic actions of ethanol or its metabolites could also be involved. Overall, the model should be useful for studying mechanisms of ethanol-induced selective cortical and olfactory brain damage.