Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus

Maria Grazia De Simoni, Carlo Perego, Teresa Ravizza, Daniela Moneta, Mirko Conti, Francesco Marchesi, Ada De Luigi, Silvio Garattini, Annamaria Vezzani

Research output: Contribution to journalArticle

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Abstract

Limbic status epilepticus was induced in rats by unilateral 60-min electrical stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR followed by Southern blot analysis, transcripts of interleukin-1β, interleukin-6, interleukin-1 receptor antagonist and inducible nitric oxide synthase were significantly increased 2 h after status epilepticus in the stimulated hippocampus. Induction was maximal at 6 h for interleukin-1β (445%), interleukin-6 (405%) and tumour necrosis factor-α (264%) and at 24 h for interleukin-1 receptor antagonist (494%) and inducible nitric oxide synthase (432%). In rats with spontaneous seizures (60 days after status epilepticus), interleukin-1β mRNA was still higher than controls (241%). Immunocytochemical staining of interleukin-1β, interleukin-6 and tumour necrosis factor-α was enhanced in glia with a time-course similar to that of the respective transcripts. Sixty days after status epilepticus, interleukin-1β immunoreactivity was increased exclusively in neurons in one third of the animals. Multiple intracerebroventricular injections of interleukin-1 receptor antagonist (0.5 μg/3 μL) significantly decreased the severity of behavioural convulsions during electrical stimulation and selectively reduced tumour necrosis factor-α content in the hippocampus measured 18 h after status epilepticus. Thus, the induction of spontaneously recurring seizures in rats involves the activation of inflammatory cytokines and related pro- and anti-inflammatory genes in the hippocampus. These changes may play an active role in hyperexcitability of the epileptic tissue.

Original languageEnglish
Pages (from-to)2623-2633
Number of pages11
JournalEuropean Journal of Neuroscience
Volume12
Issue number7
DOIs
Publication statusPublished - 2000

Fingerprint

Status Epilepticus
Interleukin-1
Hippocampus
Interleukin-1 Receptors
Cytokines
Interleukin-6
Seizures
Tumor Necrosis Factor-alpha
Genes
Nitric Oxide Synthase Type II
Electric Stimulation
Southern Blotting
Neuroglia
Anti-Inflammatory Agents
Staining and Labeling
Neurons
Polymerase Chain Reaction
Messenger RNA
Injections

Keywords

  • Interleukin-1
  • Interleukin-1 receptor antagonist
  • Interleukin-6
  • Nitric oxide synthase
  • Seizures
  • Tumour necrosis factor-α

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. / De Simoni, Maria Grazia; Perego, Carlo; Ravizza, Teresa; Moneta, Daniela; Conti, Mirko; Marchesi, Francesco; De Luigi, Ada; Garattini, Silvio; Vezzani, Annamaria.

In: European Journal of Neuroscience, Vol. 12, No. 7, 2000, p. 2623-2633.

Research output: Contribution to journalArticle

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abstract = "Limbic status epilepticus was induced in rats by unilateral 60-min electrical stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR followed by Southern blot analysis, transcripts of interleukin-1β, interleukin-6, interleukin-1 receptor antagonist and inducible nitric oxide synthase were significantly increased 2 h after status epilepticus in the stimulated hippocampus. Induction was maximal at 6 h for interleukin-1β (445{\%}), interleukin-6 (405{\%}) and tumour necrosis factor-α (264{\%}) and at 24 h for interleukin-1 receptor antagonist (494{\%}) and inducible nitric oxide synthase (432{\%}). In rats with spontaneous seizures (60 days after status epilepticus), interleukin-1β mRNA was still higher than controls (241{\%}). Immunocytochemical staining of interleukin-1β, interleukin-6 and tumour necrosis factor-α was enhanced in glia with a time-course similar to that of the respective transcripts. Sixty days after status epilepticus, interleukin-1β immunoreactivity was increased exclusively in neurons in one third of the animals. Multiple intracerebroventricular injections of interleukin-1 receptor antagonist (0.5 μg/3 μL) significantly decreased the severity of behavioural convulsions during electrical stimulation and selectively reduced tumour necrosis factor-α content in the hippocampus measured 18 h after status epilepticus. Thus, the induction of spontaneously recurring seizures in rats involves the activation of inflammatory cytokines and related pro- and anti-inflammatory genes in the hippocampus. These changes may play an active role in hyperexcitability of the epileptic tissue.",
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AU - Ravizza, Teresa

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AU - Marchesi, Francesco

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AU - Garattini, Silvio

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