title: Maternal immune activation increases seizure susceptibility in juvenile rat offspring.
abstract: Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia.
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Xin-Ting
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ji-Wen
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Lei
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ruo-Peng
authors.initials: RP
authors.lastname: Sun
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China. Electronic address: qilulbmyp@163.com.
authors.forename: Bao-Min
authors.initials: BM
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000150:complications*; D004827:Epilepsy / Q000276:immunology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000009:adverse effects / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000150:complications* / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D007608:Kainic Acid
keywords: Astrogliosis; Elevated plus maze; Lipopolysaccharide; Maternal immune activation; Seizure; Y-maze