title: TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain.
abstract: Febrile seizure (FS) is the most common seizure disorder in children, and children with FS are regarded as a high risk for the eventual development of epilepsy. Brain inflammation may be implicated in the mechanism of FS. Transient receptor potential vanilloid 1 (TRPV1) is believed to act as a monitor and regulator of body temperature. The role of inflammation in synaptic plasticity mediation indicates that TRPV1 is relevant to several nervous system diseases, such as epilepsy. Here, we report a critical role for TRPV1 in a febrile seizure mouse model and reveal increased levels of pro-inflammatory factors in the immature brain. Animals were subjected to hyperthermia for 30 min, which generates seizures lasting approximately 20 min, and then were used for experiments. To invoke frequently repetitive febrile seizures, mice are exposed to hyperthermia for three times daily at an interval of 4h between every time induced seizure, and a total of 4 days to induce. Behavioral testing for febrile seizures revealed that a TRPV1 knock-out mouse model demonstrated a prolonged onset latency and a shortened duration and seizure grade of febrile seizure when compared with wild type (WT) mice. The expression levels of both TRPV1 mRNA and protein increased after a hyperthermia-induced febrile seizure in WT mice. Notably, TRPV1 activation resulted in a significant elevation in the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and HMGB1) in the hippocampus and cortex. These data indicate that the reduction of TRPV1 expression parallels a decreased susceptibility to febrile seizures. Thus, preventative strategies might be developed for use during febrile seizures.
authors: Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Wen-Xian
authors: WX
authors: Huang
authors: Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
authors: Fang
authors: F
authors: Yu
authors: Dept of Surgery, College of Medicine, Texas A&M Health Science Center, Neuroscience Institute, Scott & White Hospital, & Central Texas Veterans Health Care System, Temple, TX, United States.
authors: Russell M
authors: RM
authors: Sanchez
authors: Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Yu-Qiang
authors: YQ
authors: Liu
authors: Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Jia-Wei
authors: JW
authors: Min
authors: Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Jiang-Jian
authors: JJ
authors: Hu
authors: Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Najeeb Bassam
authors: NB
authors: Bsoul
authors: Department of Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Song
authors: S
authors: Han
authors: Department of Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Jun
authors: J
authors: Yin
authors: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors: Wan-Hong
authors: WH
authors: Liu
authors: Department of Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address: hexiaohua@whu.edu.cn.
authors: Xiao-Hua
authors: XH
authors: He
authors: Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disorder, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address: pengbiwen@whu.edu.cn.
authors: Bi-Wen
authors: BW
authors: Peng
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism; D006979:Hyperthermia, Induced; D051379:Mice; D018345:Mice, Knockout; D003294:Seizures, Febrile / Q000276:immunology / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse
keywords: Febrile seizures; HMGB1; IL-1β; TRPV1