Abstract

Children are more likely to develop epileptic seizures (ictal discharges lasting tens of seconds) than adults. A higher predisposition of the juvenile brain to the generation of epileptiform activity is thought to be due to a prevalence of inhibition over excitation at the early stage of brain development. However, the molecular and physiological mechanisms underlying these age-related differences are yet to be clarified. We compared the ictal activity induced by a convulsant 4-aminopyridine (4-AP) in the horizontal slices of the entorhinal cortex and hippocampus of 3- and 8-week-old Wistar rats. In 3-week-old rats, the ictal discharge was always preceded by a detectable preictal activity, as manifested in one or several 3–4-s GABA-glutamate events, whereas in 8-week-old rats, such events were typically absent or very rare (no more than one occasional short event). The ictal activity resistance to external exposures was also age-dependent. In 8-week-old rats, by contrast to 3-week-old animals, ictal discharge generation in the entorhinal cortex was blocked completely and replaced by 0.2–0.3 Hz interictal activity (simultaneous 1–3-s burst discharges) by a partial blockade of KCC2 cotransporter or Na⁺–K⁺-pump, as well as by low-frequency electric stimulation. Thus, our data indicate that ictal discharges in the immature (3-week-old) brain are more resistant to external exposures than in the brain of adult rats. Interictal and ictal epileptiform activities are antagonistic in 8-week-old animals. In contrast, the appearance of interictal activity interrupts the generation of ictal discharges completely. It can therefore be considered as one of the putative antiepileptic mechanisms in the mature rat brain.

中文翻译：

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随年龄的生成癫痫样活动在4-氨基吡啶模型与大鼠内嗅皮层的切片。

摘要

儿童比成人更容易发生癫痫发作（持续放电数十秒钟）。认为幼年脑对癫痫样活动的产生具有更高的易感性，这是由于在脑发育的早期，抑制作用普遍超过了兴奋作用。但是，这些与年龄有关的差异的分子和生理机制尚待阐明。我们比较了惊厥的4-氨基吡啶（4-AP）在3和8周龄的Wistar大鼠的内嗅皮层和海马的水平切片中诱导的发作活性。在3周大的大鼠中，总是在发作前有可检测到的发作前活动，这在一个或几个3–4 s GABA-谷氨酸事件中得到了证实，而在8周大的大鼠中，此类事件通常不存在或非常罕见（偶尔发生的事件不超过一次）。对外界暴露的抵抗力也与年龄有关。与3周龄的动物相比，在8周龄的大鼠中，内嗅皮层中的眼动放电产生被完全阻断，并被0.2-0.3 Hz的室间活动（同时发生1-3s的突发放电）所代替。封锁KCC2共转运蛋白或Na⁺ –K ^{+ –}泵，以及低频电刺激。因此，我们的数据表明，与成年大鼠的大脑相比，未成熟（3周龄）的大脑中的金属放电对外部暴露的抵抗力更高。在8周龄的动物中，发作期和发作期癫痫样活动是拮抗的。相反，发作间活动的出现完全中断了发作放电的产生。因此，它可以被认为是成熟大鼠大脑中公认的抗癫痫机制之一。