Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States.
Neuroscience. 2013 Nov 12;252:45-59. doi: 10.1016/j.neuroscience.2013.07.045. Epub 2013 Jul 27.
Although hippocampal sclerosis is frequently identified as a possible epileptic focus in patients with temporal lobe epilepsy, neuronal loss has also been observed in additional structures, including areas outside the temporal lobe. The claim from several researchers using animal models of acquired epilepsy that the immature brain can develop epilepsy without evidence of hippocampal neuronal death raises the possibility that neuronal death in some of these other regions may also be important for epileptogenesis. The present study used the lithium pilocarpine model of acquired epilepsy in immature animals to assess which structures outside the hippocampus are injured acutely after status epilepticus. Sprague-Dawley rat pups were implanted with surface EEG electrodes, and status epilepticus was induced at 20 days of age with lithium pilocarpine. After 72 h, brain tissue from 12 animals was examined with Fluoro-Jade B, a histochemical marker for degenerating neurons. All animals that had confirmed status epilepticus demonstrated Fluoro-Jade B staining in areas outside the hippocampus. The most prominent staining was seen in the thalamus (mediodorsal, paratenial, reuniens, and ventral lateral geniculate nuclei), amygdala (ventral lateral, posteromedial, and basomedial nuclei), ventral premammillary nuclei of hypothalamus, and paralimbic cortices (perirhinal, entorhinal, and piriform) as well as parasubiculum and dorsal endopiriform nuclei. These results demonstrate that lithium pilocarpine-induced status epilepticus in the immature rat brain consistently results in neuronal injury in several distinct areas outside of the hippocampus. Many of these regions are similar to areas damaged in patients with temporal lobe epilepsy, thus suggesting a possible role in epileptogenesis.
尽管海马硬化症经常被认为是颞叶癫痫患者的潜在癫痫灶，但在其他结构中也观察到神经元丢失，包括颞叶以外的区域。一些使用获得性癫痫动物模型的研究人员声称，未成熟的大脑在没有海马神经元死亡证据的情况下也可能发生癫痫，这提出了一个可能性，即在这些其他区域中的神经元死亡也可能对癫痫发生很重要。本研究使用未成熟动物的锂匹罗卡品获得性癫痫模型来评估癫痫持续状态后海马体以外的哪些结构会受到急性损伤。Sprague-Dawley 幼鼠被植入表面 EEG 电极，并在 20 天大时用锂匹罗卡品诱导癫痫持续状态。72 小时后，用 Fluoro-Jade B 检查 12 只动物的脑组织，Fluoro-Jade B 是一种用于检测变性神经元的组织化学标记物。所有确认癫痫持续状态的动物在海马体以外的区域均显示 Fluoro-Jade B 染色。最明显的染色见于丘脑（mediodorsal、paratenial、reuniens 和 ventral lateral geniculate nuclei）、杏仁核（ventral lateral、posteromedial 和 basomedial nuclei）、下丘脑腹前乳头核和边缘皮层（perirhinal、entorhinal 和piriform）以及旁海马回和背内嗅核。这些结果表明，锂匹罗卡品诱导的未成熟大鼠脑癫痫持续状态一致导致海马体以外的几个不同区域的神经元损伤。这些区域中的许多与颞叶癫痫患者受损的区域相似，因此提示其在癫痫发生中的可能作用。
