Chan Woo Park1, Tae-Kyeong Lee2, Jeong Hwi Cho2, In Hye Kim2, Jae-Chul Lee2, Bich-Na Shin3, Ji Hyeon Ahn4, Sung Koo Kim5, Myoung Cheol Shin1, Taek Geun Ohk1, Jun Hwi Cho1, Moo-Ho Won2, Young Joo Lee6, Jeong Yeol Seo7, Joon Ha Park4. 1. a Department of Emergency Medicine, School of Medicine , Kangwon National University , Chuncheon , South Korea. 2. b Department of Neurobiology, School of Medicine , Kangwon National University , Chuncheon , South Korea. 3. c Department of Physiology, College of Medicine , Hallym University , Chuncheon , South Korea. 4. d Department of Biomedical Science and Research Institute for Bioscience and Biotechnology , Hallym University , Chuncheon , South Korea. 5. e Department of Pediatrics , Dongtan Sacred Heart Hospital, School of Medicine, Hallym University , Hwaseong , South Korea. 6. f Department of Emergency Medicine , Seoul Hospital, College of Medicine, Sooncheonhyang University , Seoul , South Kore. 7. g Department of Emergency Medicine , Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University , Chuncheon , South Korea.
Abstract
OBJECTIVES: Rufinamide, a voltage-gated sodium channel (VGSC) blocker, is widely used for the clinical treatment of seizures associated with Lennox-Gastaut syndrome. Previous studies have demonstrated that VGSC blockers have neuroprotective properties against ischemic damage following experimental cerebral ischemia. However, protective effects of rufinamide against cerebral ischemic insults have not been addressed. Therefore, in the present study, we firstly examined neuroprotective effects of rufinamide using a gerbil model of transient global cerebral ischemia. METHODS: Gerbils were established by the occlusion of common carotid arteries for 5 min. The gerbils were divided into vehicle-treated sham-operated group, vehicle-treated ischemia-operated group, 50 and 100 mg/kg rufinamide-treated sham-operated groups, and 50 and 100 mg/kg rufinamide-treated ischemia-operated groups. Rufinamide was administrated intraperitoneally once daily for 3 days before ischemic surgery. To examine neuroprotective effects of rufinamide, we carried out cresyl violet staining, neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, we examined gliosis using immunohistochemistry for glial fibrillary acidic protein (a marker for astrocytes) and ionized calcium-binding adapter molecule 1 (a marker for microglia). RESULTS: We found that pre-treatment with 100 mg/kg of rufinamide effectively protected pyramidal neurons in the hippocampal cornus ammonis 1 (CA1) area after transient global cerebral ischemia. In addition, pre-treatment with 100 mg/kg of rufinamide significantly attenuated activations of astrocytes and microglia in the ischemic CA1 area. DISCUSSION: These findings suggest that rufinamide can display neuroprotective effect against cerebral ischemic insults and that its neuroprotective effect may involve the attenuation of ischemia-induced glial activation.
OBJECTIVES:Rufinamide, a voltage-gated sodium channel (VGSC) blocker, is widely used for the clinical treatment of seizures associated with Lennox-Gastaut syndrome. Previous studies have demonstrated that VGSC blockers have neuroprotective properties against ischemic damage following experimental cerebral ischemia. However, protective effects of rufinamide against cerebral ischemic insults have not been addressed. Therefore, in the present study, we firstly examined neuroprotective effects of rufinamide using a gerbil model of transient global cerebral ischemia. METHODS: Gerbils were established by the occlusion of common carotid arteries for 5 min. The gerbils were divided into vehicle-treated sham-operated group, vehicle-treated ischemia-operated group, 50 and 100 mg/kg rufinamide-treated sham-operated groups, and 50 and 100 mg/kg rufinamide-treated ischemia-operated groups. Rufinamide was administrated intraperitoneally once daily for 3 days before ischemic surgery. To examine neuroprotective effects of rufinamide, we carried out cresyl violet staining, neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, we examined gliosis using immunohistochemistry for glial fibrillary acidic protein (a marker for astrocytes) and ionized calcium-binding adapter molecule 1 (a marker for microglia). RESULTS: We found that pre-treatment with 100 mg/kg of rufinamide effectively protected pyramidal neurons in the hippocampal cornus ammonis 1 (CA1) area after transient global cerebral ischemia. In addition, pre-treatment with 100 mg/kg of rufinamide significantly attenuated activations of astrocytes and microglia in the ischemic CA1 area. DISCUSSION: These findings suggest that rufinamide can display neuroprotective effect against cerebral ischemic insults and that its neuroprotective effect may involve the attenuation of ischemia-induced glial activation.
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