Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development

Massimo Rizzi, Carlo Perego, Marisa Aliprandi, Cristina Richichi, Teresa Ravizza, Daniele Colella, Jana Velískǒvá, Solomon L. Moshé, M. Grazia De Simoni, Annamaria Vezzani

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229 Scopus citations


In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal injury) to elucidate the role of cytokines in this process. Thus, we investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At PN9, there was little activation of microglia and astrocytes at any time point studied. Interleukin-1β (IL), tumor necrosis factor-α (TNF), and IL-6 or the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not increase. No evidence of cell injury has been detected. At PN15, immunostaining of microglia and astrocytes was enhanced, but only IL-1β mRNA expression was increased. These changes were observed 4 h after SE. Scattered injured neurons in CA3 and subiculum, but not in any other region, were present 24 h following SE. At PN21, immunostaining of microglia and astrocytes and the mRNA expression of all cytokines studied was significantly increased already 4 h after SE. At 24 h, many injured neurons were present in CA1 and CA3 regions and in 40% of rats in other forebrain areas. These data show that (i) the pattern of glia activation and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal injury in the hippocampus occurs only when cytokines are induced and their synthesis precedes the appearance of neuronal damage. Thus, cytokine expression in immature brain is associated specifically with cell injury rather than with seizures per se, suggesting that proinflammatory cytokines may contribute to the occurence of SE-induced hippocampal damage.

Original languageEnglish (US)
Pages (from-to)494-503
Number of pages10
JournalNeurobiology of Disease
Issue number3
StatePublished - Dec 2003


  • Brain development
  • Inflammation
  • Interleukins
  • Neurodegeneration
  • TNF-α

ASJC Scopus subject areas

  • Neurology


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