Effect of Ibuprofen on Autophagy of Astrocytes During Pentylenetetrazol-Induced Epilepsy and its Significance: An Experimental Study

Epilepsy is a chronic neurological disease. Astrogliosis is an important pathological change in epileptic lesions. Studies have reported that ibuprofen can affect autophagy and/or inhibit cell proliferation in many diseases. This study investigated the effect and significance of ibuprofen on autophagy of astrocytes during pentylenetetrazol (PTZ) induced epilepsy. 60 male Sprague-Dawley (SD) rats were randomly divided into five groups: control group (received normal saline), PTZ group, 3-methyladenine (3-MA) + PTZ group, ibuprofen + PTZ group and 3-MA + ibuprofen + PTZ group. Dose of each agent was 35 mg/kg (PTZ), 10 mg/kg (3-MA) and 30 mg/kg (ibuprofen) and all drugs were administered intraperitoneally 15 times on alternate days (29 days). Human astrocytes were cultured in vitro. Behavioral performance (i.e., latency, grade and duration of seizures) and EEG of rats were observed and recorded. Proliferation of astrocytes was detected by CCK-8 method. Immunofluorescence and Western blot test were used to detect the expression of LC3 and GFAP. Mean number, grade and duration of seizures were markedly reduced in ibuprofen + PTZ group and 3-MA + ibuprofen + PTZ group (P < 0.05). Similarly, peak of EEG waves were markedly reduced in ibuprofen + PTZ group and 3-MA + ibuprofen + PTZ group (P < 0.05). Compared to the control group, the level of LC3 in ibuprofen group was significantly increased in vitro (P < 0.05). While, levels of LC3 were significantly higher and that of GFAP were significantly lower in ibuprofen + PTZ group (P < 0.05) compared to PTZ group in vivo. Ibuprofen reduces the proliferation of astrocytes by increasing autophagy, thus affecting the development of epilepsy. Therefore, ibuprofen may be used as an adjuvant to improve efficacy of treatment in epilepsy.