title: A postnatal peak in microglial development in the mouse hippocampus is correlated with heightened sensitivity to seizure triggers.
abstract: BACKGROUND
  Explosive synaptogenesis and synaptic pruning occur in the hippocampus during the first two weeks of postnatal life, coincident with a heightened susceptibility to seizures in rodents. To determine the temporal correlation between microglial development and age-dependent susceptibility and response to seizures, we quantified developmental changes in basal microglia levels and seizure-induced microglial activation in the hippocampus of Cx3Cr1(GFP /+) transgenic mice.
  
  
  METHODS
  Basal levels of microglia were quantified in the hippocampi of Cx3Cr1(GFP /+) mice at P0, P5, P10, P15, P20, P25, P30, P40, and P60. Seizure susceptibility and seizure-induced microglial activation were assessed in response to febrile seizures (lipopolysaccharide followed by hyperthermia) and kainic acid-induced status epilepticus.
  
  
  RESULTS
  The density of microglia within the hippocampus increased rapidly after birth, reaching a peak during the second week of life - the age at which the animals became most vulnerable to seizure triggers. In addition, this peak of microglial development and seizure vulnerability during the second postnatal week represented the time of maximal seizure-induced microglia activation.
  
  
  CONCLUSIONS
  Overreactive innate immunity mediated by activated microglia may exacerbate acute injury to neuronal synapses and contribute to the long-term epileptogenic effects of early-life seizures. Anti-inflammatory therapy targeting excessive production of inflammatory mediators by activated microglia, therefore, may be an effective age-specific therapeutic strategy to minimize neuronal dysfunction and prevent increases in susceptibility to subsequent seizures in developing animals.
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Iris
authors.initials: I
authors.lastname: Kim
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Mlsna
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Stella
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Brandy
authors.initials: B
authors.lastname: Le
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yu
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago Stanley Manne Children's Research Institute Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago Illinois.
authors.forename: Sookyong
authors.initials: S
authors.lastname: Koh
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000503:physiopathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology*; D006358:Hot Temperature; D053583:Interleukin-1beta / Q000378:metabolism; D007608:Kainic Acid; D008070:Lipopolysaccharides; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D015213:Neuroimmunomodulation / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D003294:Seizures, Febrile / Q000473:pathology / Q000503:physiopathology*; D013226:Status Epilepticus / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D007608:Kainic Acid
keywords: Early life; epilepsy; febrile seizures; status epilepticus