Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain
Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain
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DOI：
10.1016/s0006-8993(00)02137-5
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发表时间：
2000-05-02
期刊：
影响因子：
2.9
通讯作者：
Schmued, LC
中科院分区：
文献类型：
--
作者：
Hopkins, KJ;Wang, GJ;Schmued, LC
兴奋性氨基酸谷氨酸与几种不同的中枢神经系统疾病相关的神经变性有关。红藻氨酸（KA），一种谷氨酸类似物，已知激活谷氨酸受体的AMPA/KA亚型，已被广泛用作癫痫模型。然而，缺乏对其神经病理学影响的长期时间研究。在这项研究中，两种技术被用来直接可视化和表征的神经病理学发生在2个月的时间后，KA诱导癫痫持续状态的成人。雌性Sprague-Dawley大鼠注射后存活时间为2、4、8 h、2天、2周或2个月。处理后4 h，在皮质、海马、丘脑、基底神经节和杏仁核内观察到Fluoro-Jade B（FJB）标记，FJB是一种荧光绿色染料，可标记退化神经元的细胞体、树突、轴突和轴突终末。梨状皮质、海马和丘脑的标记水平最高。还使用髓鞘特异性黑金（BG）染色检查KA处理后大鼠前脑中的髓鞘变化。在与FJB阳性神经元相同的区域中观察到静脉曲张的有髓鞘纤维，尽管这些变化在2小时存活时间点时是明显的。两种染色都显示了整个受影响区域的脑损伤的时间进展。治疗后2个月，可以检测到很少的变性神经元，并且在大多数区域中不存在异常髓鞘。由于髓鞘改变，aes可以在神经元变性之前看到，并且少突胶质细胞表达功能性AMPA/红藻氨酸盐型谷氨酸受体，因此神经变性和髓鞘病理学可能作为独立事件发生。因此，研究人员在设计实验时应考虑红藻氨酸的时间和多重效应，以优化其感兴趣的终点的条件。(C)2000 Elsevier Science B. V.保留所有权利。
The excitatory amino acid glutamate has been implicated in the neurodegeneration associated with several different central nervous system diseases. Treatment with kainic acid (KA), a glutamate analog known to activate the AMPA/KA subtype of glutamate receptor, has been widely used as a model of epilepsy. Long term temporal studies of its neuropathological effects, however, are lacking. In this study, two techniques were used to directly visualize and characterize the neuropathology that occurred over a 2-month period following KA-induced status epilepticus in adult. female Sprague-Dawley rats. Post-injection survival was 2, 4, 8 h, 2 days, 2 weeks, or 2 months. Labeling with Fluoro-Jade B (FJB), a fluorescent green dye that labels the cell body, dendrites, axons and axon terminals of degenerating neurons, was observed within the cortex, hippocampus, thalamus, basal ganglia, and amygdala by 4 h post-treatment. The highest level of labeling was seen in the piriform cortex, hippocampus, and thalamus. Myelin changes in the rat forebrain following KA treatment were also examined using the myelin-specific Black-Gold (BG) stain, Varicose myelinated fibers were observed in the same regions as FJB positive neurons, although these changes were evident by the 2-h survival time-point. Both stains showed a temporal progression of brain damage throughout the affected areas. By 2 months post-treatment, few degenerating neurons could be detected and abnormal myelin was absent in most regions. As myelin chan,aes can be seen prior to neuronal degeneration, and oligodendrocytes express functional AMPA/kainate-type glutamate receptors, the neurodegeneration and myelin pathologies may occur as independent events. Thus, researchers should consider the temporal and multiple effects of kainic acid to optimize conditions for their endpoint of interest when designing experiments. (C) 2000 Elsevier Science B.V. All rights reserved.