Departamento de Neurobiologia Conductual y Cognitiva, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Campus UNAM-Juriquilla, Queretaro, Mexico.
Department of Chemistry, Center for Behavioral Neuroscience, American University, Washington D.C. 20016, USA.
Neurobiol Dis. 2019 Jan;121:177-186. doi: 10.1016/j.nbd.2018.10.005. Epub 2018 Oct 7.
Epilepsy produces chronic chemical changes induced by altered cellular structures, and acute ones produced by conditions leading into individual seizures. Here, we aim to quantify 24 molecules simultaneously at baseline and during periods of lowered seizure threshold in rats. Using serial hippocampal microdialysis collections starting two weeks after the pilocarpine-induced status epilepticus, we evaluated how this chronic epilepsy model affects molecule levels and their interactions. Then, we quantified the changes occurring when the brain moves into a pro-seizure state using a novel model of physiological ictogenesis. Compared with controls, pilocarpine animals had significantly decreased baseline levels of adenosine, homovanillic acid, and serotonin, but significantly increased levels of choline, glutamate, phenylalanine, and tyrosine. Step-wise linear regression identified that choline, homovanillic acid, adenosine, and serotonin are the most important features to characterize the difference in the extracellular milieu between pilocarpine and control animals. When increasing the hippocampal seizure risk, the concentrations of normetanephrine, serine, aspartate, and 5-hydroxyindoleacetic acid were the most prominent; however, there were no specific, consistent changes prior to individual seizures.
癫痫会导致由细胞结构改变引起的慢性化学变化，以及由导致个体发作的情况引起的急性变化。在这里，我们旨在同时定量 24 种分子在基线水平和降低癫痫发作阈值期间的水平。使用在匹罗卡品诱导的癫痫持续状态后两周开始的连续海马微透析收集，我们评估了这种慢性癫痫模型如何影响分子水平及其相互作用。然后，我们使用新的生理癫痫发生模型来量化大脑进入癫痫发作状态时发生的变化。与对照组相比，匹罗卡品动物的腺苷、高香草酸和血清素的基线水平显著降低，但胆碱、谷氨酸、苯丙氨酸和酪氨酸的水平显著升高。逐步线性回归确定，胆碱、高香草酸、腺苷和血清素是表征匹罗卡品和对照组动物细胞外环境差异的最重要特征。当增加海马癫痫发作风险时，去甲肾上腺素、丝氨酸、天冬氨酸和 5-羟吲哚乙酸的浓度最为突出；然而，在个别发作之前没有特定的、一致的变化。
