Innate immune reaction in response to seizures: implications for the neuropathology associated with epilepsy

Neurobiol Dis. 2004 Jul;16(2):321-34. doi: 10.1016/j.nbd.2004.03.010.

Abstract

In the present study, the expression of pro-inflammatory transcripts was assessed across the brain of mice having undertaken pilocarpine-induced seizures. Pilocarpine-induced marked neurodegeneration and demyelination in multiple regions of the forebrain. The pattern of genes encoding toll-like receptor type 2 (TLR2) and I kappa B alpha (index of NF-kappa B activation) was associated with the neurodegenerating areas, but this was not the case for the mRNA encoding other inflammatory proteins. Scattered tumor necrosis factor-alpha (TNF-alpha)-expressing cells were found across brain, whereas the signals for monocyte-chemoattractant protein-1 and microsomal prostaglandin mPGES E synthase were robust in thalamus and cerebral cortex and weak in the hippocampus and amygdala. TLR2 and TNF-alpha transcripts were expressed mainly in microglia/macrophages. Cyclooxygenase-2 was induced specifically in the hippocampus and piriform cortex. A low increase in interleukin-12 mRNA was detected in the brain, but the signal for interferon gamma (IFN-gamma) remained undetectable. Although pro-inflammatory markers were induced in a different manner across the CNS, their patterns were not characteristic of those caused by other inflammatory challenges, such as endotoxin. These data suggest a different mechanism involved in regulating the innate immune reaction in response to seizures and could have direct implications for the neuropathology associated with epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology*
  • Brain / pathology
  • Brain / physiopathology
  • Cell Death / immunology
  • Cyclooxygenase 2
  • Cytokines / immunology
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / pathology
  • Epilepsy / chemically induced
  • Epilepsy / immunology*
  • Epilepsy / pathology*
  • Gene Expression / immunology
  • Intramolecular Oxidoreductases / genetics
  • Isoenzymes / genetics
  • Male
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred Strains
  • Muscarinic Agonists
  • Neuroimmunomodulation / immunology*
  • Neurons / pathology
  • Phenotype
  • Pilocarpine
  • Prostaglandin-E Synthases
  • Prostaglandin-Endoperoxide Synthases / genetics
  • RNA, Messenger / analysis
  • Receptors, Cell Surface / genetics
  • Toll-Like Receptor 2
  • Toll-Like Receptors

Substances

  • Cytokines
  • Isoenzymes
  • Membrane Glycoproteins
  • Muscarinic Agonists
  • RNA, Messenger
  • Receptors, Cell Surface
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Pilocarpine
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases