title: Inflammation induced at different developmental stages affects differently the range of microglial reactivity and the course of seizures evoked in the adult rat.
abstract: BACKGROUND
  In the brain, inflammation occurs following a variety of types of brain damage, including epileptic seizures. Proinflammatory cytokines, like IL-1β or TNFα, can increase neuronal excitability and initiate spontaneous seizures or epileptogenesis. Recent studies indicate that the effects can be attenuated or even abolished in animals subjected to inflammation-inducing treatments at earlier developmental stages, termed "preconditioning". Immunocompetent microglial cells display particular sensitivity to subtle brain pathologies showing a morphological continuum from resting to reactive forms. Following inflammation, multiple ramified processes of resting microglia become gradually shorter, and the cells transform into macrophages. Parameters of the morphological variations were used here as indicators of the nervous tissue reactivity to seizures in adult rats experiencing inflammation at earlier stages of postnatal development.
  
  
  METHODS
  Systemic inflammation was induced with lipopolysaccharide (LPS) in 6-day-old or 30-day-old rats. In two-month-old survivors of the inflammatory status, seizures were evoked with pilocarpine injection. The seizure intensity was scored during a six-hour continuous observation period following the injection. Brain sections were immunostained for Iba1 to visualize microglia. Thereafter, morphology of microglial cells located in the hippocampal formation was analyzed using parameters such as solidity, circularity, ramification index, and area.
  
  
  RESULTS
  In naïve rats, seizure-induced transformations of microglial cells were reflected by strong changes in the parameters of their morphology. However, in the adult rats pretreated with LPS on their 6th or 30th postnatal days, the seizure-induced changes were significantly reduced, and microglial morphology remained significantly closer to normal. Significant amelioration of the acute phase of seizures was observed only when inflammation was induced in 30-day-old, but not in 6-day-old, rats.
  
  
  CONCLUSIONS
  The results confirm previous reports that moderate inflammation protects the nervous tissue from subsequent damage by reducing influences of proinflammatory factors on reactive glial cells. The young-age inflammation may have age-dependent effects on susceptibility to seizures induced in adulthood. This article is part of a Special Issue entitled "Status Epilepticus".
authors.affiliation: Department of Neuroanatomy, Institute of Zoology, Jagiellonian University, 9 Gronostajowa St., 30-387 Kraków, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Kosonowska
authors.affiliation: Department of Neuroanatomy, Institute of Zoology, Jagiellonian University, 9 Gronostajowa St., 30-387 Kraków, Poland. Electronic address: kjjaneczko@gmail.com.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Janeczko
authors.affiliation: Department of Neuroanatomy, Institute of Zoology, Jagiellonian University, 9 Gronostajowa St., 30-387 Kraków, Poland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Setkowicz
mesh_terms: D000367:Age Factors; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D010862:Pilocarpine
keywords: Cell morphology; Epileptogenesis; Iba1; Immunohistochemistry; Lipopolysaccharide; Pilocarpine