Xenon has been shown to have neuroprotective effects and is clinically used as a favorable safe inhalation anesthetic. We previously confirmed the neuroprotective effects of xenon treatment in epileptic animals. However, the mechanism underlying these protective effects remains unclear. We aimed to assess the effects of xenon inhalation on autophagy in neuronal injury induced by acute generalized seizures. Kainic acid (KA) was injected into the lateral ventricle of male Sprague–Dawley rats to induce acute generalized seizures. Next, the rats were treated via inhalation of a 70% xenon/21% oxygen/9% nitrogen mixture for 60 min immediately after KA administration. The control group was treated via inhalation of a 79% nitrogen/21% oxygen mixture. Subsequently, two inhibitors (3-methyladenine or bafilomycin A₁) or an autophagy inducer (rapamycin) were administered, respectively, before KA and xenon administration to determine the role of autophagy in the protective effects of xenon. The levels of apoptosis, neuronal injury, and autophagy were determined in all the rats. Xenon inhalation significantly attenuated the severity of the seizure-induced neuronal injury. Increased autophagy accompanied this inhibitive effect. Autophagy inhibition eliminated these xenon neuroprotective effects. A simulation of autophagy using rapamycin recapitulated xenon’s protective effects on KA-induced acute generalized seizures in the rats. These findings confirmed that xenon exerts strong neuroprotective effects in KA-induced acute generalized seizures. Further, they indicate that increased autophagy may underlie the protective effects of xenon. Therefore, xenon and autophagy inducers may be useful clinical options for their neuroprotective effects in epileptic seizures.

氙气已被证明具有神经保护作用，并在临床上被用作一种安全的安全吸入麻醉剂。我们先前确认了氙气治疗癫痫动物的神经保护作用。但是，这些保护作用的机制尚不清楚。我们旨在评估氙气吸入对急性全身性癫痫发作所致神经元损伤中自噬的影响。将海藻酸（KA）注入雄性Sprague-Dawley大鼠的侧脑室，以诱发急性全身性癫痫发作。接下来，对大鼠进行治疗通过KA施用后立即吸入70％氙/ 21％氧气/ 9％氮气的混合物60分钟。对照组接受治疗通过吸入79％的氮气/ 21％的氧气的混合物。随后，使用两种抑制剂（3-甲基腺嘌呤或巴氟霉素A ₁分别在KA和氙气给药之前分别施用）或自噬诱导剂（雷帕霉素），以确定自噬在氙气保护作用中的作用。测定所有大鼠的凋亡，神经元损伤和自噬水平。氙气吸入可显着减轻癫痫发作诱发的神经元损伤的严重程度。自噬增加伴随这种抑制作用。自噬抑制消除了这些氙神经保护作用。雷帕霉素自噬的模拟概括了氙气对KA诱导的大鼠急性全身性癫痫发作的保护作用。这些发现证实氙在KA诱导的急性全身性癫痫发作中具有强大的神经保护作用。此外，它们表明自噬的增加可能是氙的保护作用的基础。因此，