Department of Neurosurgery, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, China (mainland).
Clinical Experimental Center, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, China (mainland).
Med Sci Monit. 2020 Jul 20;26:e923919. doi: 10.12659/MSM.923919.
BACKGROUND Post-traumatic epilepsy (PTE) is a common type of acquired epilepsies secondary to traumatic brain injury (TBI), accounting for approximately 10-25% of patients. The present study evaluated activity of PP-4-one against mTOR signaling activation in a rat model of FeCl₂-induced post-traumatic epilepsy. MATERIAL AND METHODS Epilepsy in rats was induced by injecting 10 µl FeCl₂ (concentration 100 mM) at a uniform rate of 1 µl/minute. The iNOS expression was detected using a Leica microscope connected to a digital camera system. Reverse transcription polymerase chain reaction (RT‑PCR) was used for determination of NR1 mRNA expression. RESULTS The post-traumatic epilepsy induced neuronal degeneration in the hippocampus and frontal cortex of the rats. Treatment with PP-4-one prevented neuronal degeneration in the hippocampus and frontal cortex in rats with post-traumatic epilepsy. The data revealed markedly higher levels of p-mTOR and p-P70S6K in rat hippocampal tissues after induction of traumatic epilepsy. Treatment of post-traumatic epilepsy rats with PP-4-one significantly suppressed p-mTOR and p-P70S6K expression, and PP-4-one treatment reduced epileptic brain injury in the rats with post-traumatic epilepsy. CONCLUSIONS PP-4-one exhibits an anti-epileptogenic effect in the rat model of PTE by inhibiting behavioral seizures through suppression of iNOS and astrocytic proliferation. Moreover, PP-4-one treatment suppressed NR1 expression and targeted the mTOR pathway in PTE-induced rats. Thus, PP-4-one shows promise as a novel and effective therapeutic agent for treatment of epilepsy induced by PTE.
创伤后癫痫（PTE）是一种常见的获得性癫痫，继发于创伤性脑损伤（TBI），约占患者的 10-25%。本研究评估了 PP-4-one 在氯化亚铁诱导的创伤后癫痫大鼠模型中对 mTOR 信号激活的活性。
通过以 1µl/min 的均匀速率向大鼠注射 10µl 浓度为 100mM 的 FeCl₂来诱导癫痫。使用 Leica 显微镜连接到数字相机系统检测 iNOS 表达。逆转录聚合酶链反应（RT-PCR）用于测定 NR1 mRNA 表达。
创伤后癫痫导致大鼠海马和额皮质神经元变性。PP-4-one 治疗可预防创伤后癫痫大鼠海马和额皮质的神经元变性。数据显示，创伤性癫痫诱导后大鼠海马组织中 p-mTOR 和 p-P70S6K 水平明显升高。用 PP-4-one 治疗创伤后癫痫大鼠可显著抑制 p-mTOR 和 p-P70S6K 的表达，PP-4-one 治疗可减轻创伤后癫痫大鼠的癫痫性脑损伤。
PP-4-one 通过抑制 iNOS 和星形胶质细胞增殖抑制行为性癫痫发作，在 PTE 大鼠模型中表现出抗癫痫发生作用。此外，PP-4-one 治疗抑制了 PTE 诱导大鼠中 NR1 的表达并靶向 mTOR 通路。因此，PP-4-one 有望成为治疗 PTE 诱导的癫痫的一种新型有效治疗剂。
