THE FUNCTIONAL-ANATOMY AND PATHOLOGY OF LITHIUM PILOCARPINE AND HIGH-DOSE PILOCARPINE SEIZURES
THE FUNCTIONAL-ANATOMY AND PATHOLOGY OF LITHIUM PILOCARPINE AND HIGH-DOSE PILOCARPINE SEIZURES
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DOI：
10.1016/0306-4522(87)90171-0
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发表时间：
1987-12-01
期刊：
影响因子：
3.3
通讯作者：
ZORUMSKI, CF
中科院分区：
文献类型：
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作者：
CLIFFORD, DB;OLNEY, JW;ZORUMSKI, CF
用低剂量的锂和匹罗卡品或高剂量的匹罗卡品皮下治疗大鼠会导致严重的癫痫-脑损伤综合征。用多深度电极、定量[14C]2-脱氧葡萄糖放射自显影、光镜和电镜对治疗后的大鼠进行研究。接受锂-匹洛卡平治疗的大鼠在行为学、电图、代谢或组织病理学方面与高剂量匹洛卡平治疗的大鼠没有差异，但锂-匹洛卡平治疗的大鼠更可靠地再现了这种综合征，而且急性死亡率更低。有组织的电痉挛活动发生在行为性前肢阵挛发作之前，似乎起源于前脑腹侧苍白球和/或伏隔核附近的前脑腹侧。活动从这些地点迅速蔓延到其他地区。一旦发作，电痉挛持续数小时。在持续癫痫发作期间，大多数脑区葡萄糖利用率增加。其中，大脑皮层前部、苍白球、海马、内嗅皮层、杏仁核、外侧隔、黑质、丘脑腹基底和中背侧以及额叶运动皮层的神经元数量增加最多。持续癫痫发作的动物表现为弥散性神经变性，不涉及苍白球或腹侧苍白球，但与上述葡萄糖利用增强的模式一致。脑损伤模式与已知高毒蕈碱胆碱能受体密度区域之间没有一致的相关性。超微结构上，细胞病理改变，如与其他各种持续发作综合征相关的，类似于已知谷氨酸引起的兴奋毒性损伤。这种癫痫-脑损伤综合征与全身性kainic酸引起的症状在行为上相似，但在电生理或代谢表现上不同。在卡因酸发作期间，电图变化首先记录在海马体中，而在匹罗卡平发作时，电图变化首先在前脑腹侧区域检测到。匹洛卡品还能诱导未被桂酸激活的前脑腹侧部位的代谢激活。与这两种综合征相关的细胞病理学在类型上是相同的，但在模式上不同，胆碱能模型的特点是更大的新皮层和稍少的海马损伤。对这些胆碱能模型的进一步研究可能为主要兴奋性神经递质系统（胆碱能和谷氨酰胺）在边缘癫痫中的作用提供新的见解。
Subcutaneous treatment of rats with low doses of lithium and pilocarpine or a high dose of pilocarpine results in a severe seizure-brain damage syndrome. Rats thus treated were studied with multiple-depth electrodes, quantitative [14C]2-deoxyglucose autoradiography, and light and electron microscopy. Rats receiving lithium-pilocarpine did not differ from high-dose pilocarpine rats in behavioral, electrographic, metabolic or histopathological findings, but lithium-pilocarpine reproduced the syndrome more reliably and with a lower acute mortality rate. Organized electrographic seizure activity developed just prior to the onset of behavioral forelimb clonus and appeared to originate from ventral forebrain in the vicinity of the ventral pallidum and/or nucleus accumbens. From these sites activity spread rapidly to involve other regions. Once initiated, electrographic seizures persisted for hours. Increased glucose utilization was found in most brain regions during the period of continuous seizure activity. The greatest increases were found in the ventral pallidum, globus pallidus, hippocampus, entorhinal cortex, amygdala, lateral septum, substantia nigra, ventrobasal and mediodorsal thalamus and frontal motor cortex. Animals sustaining seizures displayed a disseminated pattern of neural degeneration not involving globus pallidus or ventral pallidum but otherwise coinciding with the above pattern of enhanced glucose utilization. No consistent correlation was observed between the pattern of brain damage and known regions of high muscarinic cholinergic receptor density. Ultrastructurally, the cytopathological changes, like those associated with various other sustained seizure syndromes, resemble the excitotoxic type of damage glutamate is known to cause. This seizure-brain damage syndrome and that induced by systemic kainic acid appear to be similar in behavioral but not in electrophysiological or metabolic manifestations. During kainic acid seizures, electrographic changes are first recorded in the hippocampus while they are first detected in the ventral forebrain region in pilocarpine seizures. Pilocarpine also induced metabolic activation of ventral forebrain sites not activated by kainic acid. The cytopathology associated with the two syndromes is identical in type but not in pattern, the cholinergic model being characterized by much greater neocortical and slightly less hippocampal damage. Further study of these cholinergic models may provide new insights into the roles of the major excitatory neurotransmitter systems (cholinergic and glutamergic) in limbic epilepsy.