An-Feng Tao1, Zheng-Hao Xu1,2, Bin Chen1, Yi Wang1, Xiao-Hua Wu1, Jing Zhang1, Yang-Shun Tang1, Ceng-Lin Xu1, Hua-Wei Zhao1, Wei-Wei Hu1, Li-Yun Shi3, Shi-Hong Zhang1, Zhong Chen1. 1. Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 2. College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. 3. Department of Basic Medical Science, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Abstract
AIMS: The postictal suppression (PS) is a common and important period following an epileptic seizure but has not been well studied. This study was designed to determine whether interleukin-1β (IL-1β) is involved in the PS. METHODS: The effects of IL-1β on the PS were tested in three independent seizure models induced by hippocampal kindling, maximal electroshock seizure (MES), and 4-aminopyridine, respectively. RESULTS: IL-1R1 knockout or IL-1RA enhanced the seizure refractory phenomenon without influencing the baseline seizure threshold in intermittent MES model. IL-1β attenuated the seizure refractory phenomenon without affecting the severity of the preceding seizures in hippocampal kindling model, while IL-1RA enhanced it. Besides, IL-1β reduced the postictal EEG suppression period, while IL-1RA prolonged it. And IL-1β showed no further effect on the postictal EEG suppression and seizure refractory phenomenon in IL-1R1 knockout mice. In addition, 30 min after intrahippocampal injection of 4-aminopyridine, IL-1β increased the incidence of SE, while IL-1RA prolonged the intervals between recurrent seizures. CONCLUSIONS: This study provides the first direct evidence that IL-1β is key regulatory factor for the PS, and its receptor IL-1R1 may be a potential target for adjuvant treatment of postictal problems.
AIMS: The postictal suppression (PS) is a common and important period following an epilepticseizure but has not been well studied. This study was designed to determine whether interleukin-1β (IL-1β) is involved in the PS. METHODS: The effects of IL-1β on the PS were tested in three independent seizure models induced by hippocampal kindling, maximal electroshock seizure (MES), and 4-aminopyridine, respectively. RESULTS:IL-1R1 knockout or IL-1RA enhanced the seizure refractory phenomenon without influencing the baseline seizure threshold in intermittent MES model. IL-1β attenuated the seizure refractory phenomenon without affecting the severity of the preceding seizures in hippocampal kindling model, while IL-1RA enhanced it. Besides, IL-1β reduced the postictal EEG suppression period, while IL-1RA prolonged it. And IL-1β showed no further effect on the postictal EEG suppression and seizure refractory phenomenon in IL-1R1 knockout mice. In addition, 30 min after intrahippocampal injection of 4-aminopyridine, IL-1β increased the incidence of SE, while IL-1RA prolonged the intervals between recurrent seizures. CONCLUSIONS: This study provides the first direct evidence that IL-1β is key regulatory factor for the PS, and its receptor IL-1R1 may be a potential target for adjuvant treatment of postictal problems.
Authors: Adam L Numis; Audrey Foster-Barber; Xutao Deng; Elizabeth E Rogers; A James Barkovich; Donna M Ferriero; Hannah C Glass Journal: Pediatr Res Date: 2019-06-24 Impact factor: 3.756