Innate immune reaction in response to seizures: implications for the neuropathology associated with epilepsy.
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.
Turrin
Nicolas P
NP
Laboratory of Molecular Endocrinology, Department of Anatomy and Physiology, CHUL Research Center, Laval University, Quebec, Canada G1V 4G2.
Rivest
Serge
S
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000276:immunology; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology; D004827:Epilepsy / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D015870:Gene Expression / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018721:Muscarinic Agonists; D015213:Neuroimmunomodulation / Q000276:immunology*; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D010862:Pilocarpine; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D016207:Cytokines; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D018721:Muscarinic Agonists; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D010862:Pilocarpine; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases