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