Pro-inflammatory cytokines, but not brain- and extracellular matrix-derived proteins, are increased in the plasma following electrically induced kindling of seizures

Abstract

BackgroundThe aim of the study was to evaluate the brain-derived proteins, extracellular matrix-derived protein and cytokines as potential peripheral biomarkers of different susceptibility to seizure development in an animal model of epilepsy evoked by chronic focal electrical stimulation of the brain.MethodsThe plasma levels of IL-1β (interleukin 1β), IL-6 (interleukin 6), UCH-L1 (ubiquitin C-terminal hydrolase 1), MMP-9 (matrix metalloproteinase 9), and GFAP (glial fibrillary acidic protein) were assessed. The peripheral concentrations of the selected proteins were analyzed according to the status of kindling and seizure severity parameters. In our study, increased concentrations of plasma IL-1β and IL-6 were observed in rats subjected to hippocampal kindling compared to sham-operated rats.ResultsAnimals that developed tonic–clonic seizures after the last stimulation had higher plasma concentrations of IL-1β and IL-6 than sham-operated rats and rats that did not develop seizure. Elevated levels of IL-1β and IL-6 were observed in rats that presented more severe seizures after the last five stimulations compared to sham-operated animals. A correlation between plasma IL-1β and IL-6 concentrations was also found. On the other hand, the plasma levels of the brain-derived proteins UCH-L1, MMP-9, and GFAP were unaffected by kindling status and seizure severity parameters.ConclusionsThe plasma concentrations of IL-1β and IL-6 may have potential utility as peripheral biomarkers of immune system activation in the course of epilepsy and translational potential for future clinical use. Surprisingly, markers of cell and nerve ending damage (GFAP, UCH-L1 and MMP-9) may have limited utility.