title: Dysfunction of thermoregulation contributes to the generation of hyperthermia-induced seizures.
abstract: Febrile seizures (FS) are generally defined as seizures taking place during fever. Long-term prognosis, including development of epilepsy and malformation of cognitive function, has been demonstrated after infantile FS. However, the mechanism that triggers seizures in hyperthermic environment is still unclear. We here found that the body temperature of rat pups that experienced experimental FS was markedly decreased (∼28°C) after they were removed from the hyperthermic environment. Both the seizure generation and the temperature drop after seizure attack were abolished by either pre-treatment with chlorpromazine (CPZ), which impairs the thermoregulation, or by an electrolytic lesion of the preoptic area and anterior hypothalamus (PO/AH). However, the non-steroidal anti-inflammatory drug celecoxib did not affect the seizure incidence and the decrease in body temperature after seizure attack. In addition, pentobarbital prevented the generation of seizures, but did not reverse the decrease of body temperature after FS. Therefore, our work indicates that an over-regulation of body temperature occurs during hyperthermic environment, and that the dysfunction of thermoregulation in the PO/AH following hyperthermia contributes to the generation of FS.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yang-Shun
authors.initials: YS
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yun-Jian
authors.initials: YJ
authors.lastname: Dai
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ceng-Lin
authors.initials: CL
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiang-Nan
authors.initials: XN
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: huww@zju.edu.cn.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address: chenzhong@zju.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000503:physiopathology*; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology / Q000627:therapeutic use; D005334:Fever / Q000150:complications / Q000503:physiopathology*; D010424:Pentobarbital / Q000494:pharmacology / Q000627:therapeutic use; D011301:Preoptic Area / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*
chemical_list: D000927:Anticonvulsants; D010424:Pentobarbital; D002746:Chlorpromazine
keywords: Body temperature; Febrile seizure; Hyperthermia; PO/AH; Thermoregulation