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皮质微脑回 Wistar 听源性大鼠的类失神发作、皮质振荡异常和焦虑样行为减少。

Absence-like Seizures, Cortical Oscillations Abnormalities and Decreased Anxiety-like Behavior in Wistar Audiogenic Rats with Cortical Microgyria.

机构信息

Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab.), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil; Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil.

Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab.), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil.

出版信息

Neuroscience. 2022 Sep 15;500:26-40. doi: 10.1016/j.neuroscience.2022.07.032. Epub 2022 Aug 4.

Abstract

Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). An approach to increment epileptogenesis and SES is to use a second insult to be added to the genetic background. Here, we used adult naïve WARs with microgyria induced by neonatal cortical freeze-lesion (FL) to evaluate the occurrence of SES and the modification in cortical oscillation patterns and behavior. The neonatal cortical FL was performed in Wistar and naïve WARs (Wis-FL and WAR-FL). Sham animals were used as controls (Wistar-S and WAR-S). Video-EEG recordings and behavioral tasks were performed during adulthood. Surprisingly, spike-waive discharges (SWD) events associated with behavior arrest were detected in WAR-S rats. Those events increased in duration and number in WAR-FL animals. The EEG quantitative analysis showed decreased power of cortical delta, theta and beta oscillations in WAR-S, decreased power of cortical fast gamma (FG) oscillations in WARs, independent of microgyria, and decreased interhemispheric synchrony for delta and FG with stronger coupling in delta and theta-FG oscillations in FL animals. The WARs, regardless of microgyria, had reduced locomotor activity, but only WAR-FL animals had reduced anxiety-like behavior. Microgyria in naïve WARs intensified SWD events associated with behavior arrest that could reflect absence-like seizures and abnormal cortical oscillations, and reduced anxiety-like behavior indicating that WAR-FL could be a reliable model to study epileptogenesis.

摘要

Wistar 听觉惊厥大鼠(WAR)是一种易感性内源性啮齿动物品系,易受急性听觉刺激诱导的癫痫发作。然而,在已点燃的 WAR 动物中并未报道自发性癫痫发作(SES)及其相关的脑电图(EEG)异常。未接受过声音诱导的 WAR 也是如此。增加癫痫发生和 SES 的一种方法是在遗传背景中添加第二种刺激。在这里,我们使用了因新生儿皮质冷冻损伤(FL)而产生微小脑回的成年新生 WAR 来评估 SES 的发生以及皮质振荡模式和行为的改变。在 Wistar 和新生 WAR(Wis-FL 和 WAR-FL)中进行了新生儿皮质 FL。假手术动物用作对照(Wistar-S 和 WAR-S)。在成年期进行视频-EEG 记录和行为任务。令人惊讶的是,在 WAR-S 大鼠中检测到与行为停止相关的尖峰波放电(SWD)事件。这些事件在 WAR-FL 动物中持续时间和数量增加。EEG 定量分析显示,WAR-S 的皮质 delta、theta 和 beta 振荡功率降低,WAR 中的皮质快 gamma(FG)振荡功率降低,与微小脑回无关,且 delta 和 FG 的大脑半球间同步性降低,FL 动物的 delta 和 theta-FG 振荡中耦合增强。WAR 无论是否有微小脑回,运动活动均减少,但只有 WAR-FL 动物焦虑样行为减少。新生 WAR 中的微小脑回加剧了与行为停止相关的 SWD 事件,这可能反映出类似于失神发作和异常皮质振荡,并伴有焦虑样行为减少,表明 WAR-FL 可能是研究癫痫发生的可靠模型。

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