title: Intraperitoneal injection of IL-4/IFN-γ modulates the proportions of microglial phenotypes and improves epilepsy outcomes in a pilocarpine model of acquired epilepsy.
abstract: Recent studies have reported microglia that are activated in the central nervous system (CNS) in patients with temporal lobe epilepsy and animal models of epilepsy. However, limited data are available on the dynamic changes of the proportions of various phenotypes of microglia throughout epileptogenesis and whether IL-4/IFN-γ administration can modulate the proportions of microglial phenotypes to affect the outcome of epilepsy. The current study examined this issue using a mouse model of pilocarpine-induced epilepsy. Flow cytometry showed that classically activated microglia (M1) and alternatively activated microglia (M2) underwent variations throughout the stages of epileptogenesis. The altered trends in the microglia-associated cytokines IL-1β, IL-4, and IL-10 paralleled the changes in phenotype proportions. We found that intraperitoneal injections of IL-4 and IFN-γ, which have been reported to modulate the phenotypes of microglia in vitro, also affected the proportion of microglia in vivo. In addition, correctly timing the modulation of the proportion of microglia improved the outcomes of epilepsy based on the reduced frequency, duration, and severity of spontaneous recurrent seizures (SRS) and increased the performances of the mice in the Morris water maze. This study is the first to report altering the proportion of microglial phenotypes in pilocarpine-induced epileptogenesis. Intraperitoneal injection of IL-4/IFN-γ could be used to modulate the proportions of the types of microglia, and epilepsy outcomes could be improved by correctly timing this modulation of phenotypes.
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Song
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Department of Neurology, Children's Hospital of Chongqing Medical University, 136# Zhongshan 2 Road, Chongqing 400014, China.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Department of Neurology, Children's Hospital of Chongqing Medical University, 136# Zhongshan 2 Road, Chongqing 400014, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xie
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hengsheng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Lab of Pediatric Neurology, Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Department of Neurology, Children's Hospital of Chongqing Medical University, 136# Zhongshan 2 Road, Chongqing 400014, China. Electronic address: dr.jiangli@yahoo.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D007155:Immunologic Factors / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D018697:Nootropic Agents / Q000008:administration & dosage; D010862:Pilocarpine; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D007155:Immunologic Factors; D053583:Interleukin-1beta; D018697:Nootropic Agents; D011994:Recombinant Proteins; D010862:Pilocarpine; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Epilepsy; IFN-γ; IL-4; M1; M2; Microglia