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

Abstract

Background The 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. Methods The 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. Results Animals 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. Conclusions The 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.

Cattle Bile Arisaema Aqueous Extracts Protect Against Febrile Seizures in Rats Through Regulating Neurotransmitters and Suppressing Neuroinflammation

“…In vivo and in vitro experiments suggest that BDNF displays an epileptogenic nature by increasing neuronal excitability ( Jakobsen et al, 2016 ; Nowroozi et al, 2021 ). GFAP is primarily distributed in astrocytes of the central nervous system and is a crucial marker of astrocyte activation ( Chmielewska et al, 2021 ). The expression of GFAP increases in the process of neurological disorders related to seizure generation ( Martinian et al, 2009 ).…”

Matrix Metalloproteinase-9 Contributes to Epilepsy Development after Ischemic Stroke in Mice

“…Elevated MMP-9 levels, often linked to pathological conditions like post-stroke epilepsy, position it as a valuable biomarker for predicting the development of epilepsy. Tracking MMP-9 levels in serum has the potential to contribute to early detection, prognosis, and evaluation of therapeutic responses across various forms of epilepsy, establishing it as a promising biomarker in clinical diagnostics [30][31][32].…”

Curcumin Lowers the Accelerated Speed of Epileptogenesis by Traumatic Brain Injury

“…TBI stimulates the secretion of the inflammatory cytokines, mainly IL-1β, which is a critical inflammatory mediator involved in PTE [ 24 ] . IL-1β is also involved in microglia/astrocyte function, distraction of BBB, and cytokine release [ 25 ] . Within a period after TBI, astrocytes are activated, and a high expression of GFAP is observed [ 24 ] .…”