Epilepsy is one of the most common neurological diseases. It adversely affects cognitive function. Neuroinflammation has been widely recognized as an important factor involved in the pathophysiology of epilepsy. Cyclooxygenase (COX) is a type of oxidoreductase enzyme that acts in the metabolic pathway converting arachidonic acid to prostaglandins, which mediate inflammatory reactions. The activation of inducible cyclooxygenase-2 (COX-2) is considered to be a precipitating factor of neuroinflammation in the brain. Neuroinflammatory processes in the brain are known to contribute to the cascade of events leading to neuronal injury, which may consequently cause cognitive decline. Here in this study, we showed that pentylenetetrazole (PTZ)-kindled mice exhibited an increased level of COX-2 and its main product prostaglandin E2 (PGE₂) along with neuroinflammation and neuronal injury in the hippocampus. Pharmacological inhibition of COX-2 by celecoxib, however, significantly reduced hippocampal neuroinflammation and neuronal injury. Furthermore, inhibition of COX-2 by celecoxib attenuated cognitive impairment in the PTZ-kindled mice, suggesting that COX-2-PGE₂ signaling pathway mediated neuroinflammation and neuronal injury contributes to cognitive dysfunction in the PTZ-kindled epilepsy mice. Targeting COX-2-PGE₂ signaling pathway in the epileptic brain appears to be a viable strategy for attenuating neuronal injury and preventing cognitive deficits in epilepsy patients.

癫痫病是最常见的神经系统疾病之一。它不利地影响认知功能。神经炎症已被广泛认为是癫痫的病理生理学中的重要因素。环氧合酶（COX）是一种氧化还原酶，在代谢途径中起作用，将花生四烯酸转化为前列腺素，从而介导炎症反应。诱导型环氧合酶2（COX-2）的激活被认为是大脑神经炎症的促发因素。已知大脑中的神经炎症过程会导致导致神经元损伤的一系列事件，从而可能导致认知能力下降。在此研究中，我们显示了戊四氮（PTZ）点燃的小鼠表现出升高的COX-2水平及其主要产物前列腺素E2（PGE₂）以及海马的神经炎症和神经元损伤。然而，塞来昔布对COX-2的药理抑制作用显着降低了海马神经炎症和神经元损伤。此外，塞来昔布对COX-2的抑制作用减弱了PTZ致癫痫小鼠的认知障碍，这表明COX-2-PGE ₂信号通路介导的神经炎症和神经元损伤导致PTZ致癫痫小鼠的认知功能障碍。在癫痫脑中靶向COX-2-PGE ₂信号通路似乎是减轻癫痫患者神经元损伤和预防认知缺陷的可行策略。