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成体 Sprague-Dawley 大鼠的棘波放电及其在颞叶癫痫动物模型中的意义。

Spike-wave discharges in adult Sprague-Dawley rats and their implications for animal models of temporal lobe epilepsy.

机构信息

Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; The Sackler Institute of Biomedical Sciences, New York University Langone Medical Center, New York, NY 10016, USA.

Department of Neurology, New York University Langone Medical Center, New York, NY 10016, USA.

出版信息

Epilepsy Behav. 2014 Mar;32:121-31. doi: 10.1016/j.yebeh.2014.01.004. Epub 2014 Feb 15.

Abstract

Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. Genetic absence epilepsy rats of Strasbourg (GAERS) and Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence, but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies using the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2- to 3-month-old naive female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest, which continued for months. Males exhibited SWDs only after 3 months of age, consistent with previous reports (Buzsáki et al., 1990). Housing in atypical lighting during early life appeared to facilitate the incidence of SWDs. Spike-wave discharges were often accompanied by behaviors similar to stage 1-2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to that of hippocampal theta rhythm during exploration for a given animal, typically 7-8 Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250 Hz) during SWDs, suggesting that neuronal activity in the hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal, and cortical neurons do not prevent SWDs, at least in this animal model. The results suggest that it is possible that SWDs occur in rodent models of TLE and that investigators mistakenly assume that they are stage 1-2 limbic seizures. We discuss the implications of the results and ways to avoid the potential problems associated with SWDs in animal models of TLE.

摘要

棘波放电(SWD)是一种丘脑皮质振荡,通常被认为是失神发作的脑电图相关物。斯特拉斯堡遗传失神癫痫大鼠(GAERS)和里夫斯堡的 Wistar 白化 Glaxo 大鼠(WAG/Rij)表现出 SWD,被认为是失神癫痫的遗传动物模型。然而,据报道,其他大鼠品系也有 SWD,这表明 SWD 的发生率可能有所不同,但所有大鼠都有发生 SWD 的倾向。这很重要,因为许多这些大鼠品系被用于研究颞叶癫痫(TLE),在那里假定对照中没有类似发作的活动。在使用 Sprague-Dawley 大鼠(一种常用于 TLE 动物模型的常见大鼠品系)进行的其他研究过程中,我们发现大约 19%的 2-3 月龄的未成熟雌性 Sprague-Dawley 大鼠在行为抑制期间会自发出现 SWD,这种情况会持续数月。雄性大鼠只有在 3 个月大后才会出现 SWD,这与之前的报道一致(Buzsáki 等人,1990)。在生命早期采用非典型光照的饲养方式似乎会促进 SWD 的发生。SWD 通常伴随着类似于 1-2 级边缘性发作的行为。因此,进行了额外的分析以解决相似性问题。我们观察到,对于给定的动物,SWD 的频率类似于其在探索过程中的海马 theta 节律,通常为 7-8 Hz。因此,在冻结行为期间发生的 theta 节律的活动不一定反映发作。在 SWD 期间,海马记录显示出高频振荡(>250 Hz),这表明海马神经元活动在 SWD 期间发生,即它不是一个被动结构。数据还表明,如果高频振荡是有节奏的,则可能反映 SWD。我们还使用雌性 Sprague-Dawley 大鼠在常见的 TLE 动物模型,匹鲁卡品模型中证实了 SWD 的存在。因此,至少在这种动物模型中,丘脑、海马和皮质神经元的损伤及其相关变化并不能阻止 SWD 的发生。研究结果表明,SWD 可能发生在 TLE 的啮齿动物模型中,研究人员错误地认为它们是 1-2 级边缘性发作。我们讨论了这些结果的意义以及避免 TLE 动物模型中与 SWD 相关的潜在问题的方法。

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