Seizure-induced changes in cytokine expression and dysregulation of plasminogen activation and IGF systems following kainic acid administration in rats

Excessive neuronal activity during epileptic seizures initiates a cascade of pathological processes. Seizures alter the expression of numerous proteins, including pro- and anti-inflammatory cytokines, growth factors, chemokines, and proteolytic enzymes. This dysregulation of signaling and regulatory molecules may contribute to epileptogenesis, drug resistance, and comorbidities by affecting neuronal excitability, synaptic plasticity, astrocyte function, blood-brain barrier integrity, and neuronal survival.In this study, we investigated changes in cytokine and protein expression in a rat model of kainic acid (KA)-induced seizures 24 hours after intrahippocampal KA administration. Using a rat cytokine array kit for initial semiquantitative screening, we identified target proteins for subsequent quantitative ELISA analysis. We further examined mRNA expression of these targets and their associated proteins in hippocampal and cortical tissues.Our results demonstrated significant upregulation of key components of the plasminogen activation system (Serpine1, Plat, and Plaur) in both hippocampus and cortex, with the hippocampal changes in the expression correlating with seizure severity. We also observed disruption of the IGF system, characterized by decreased IGFBP-5 protein levels in the hippocampus and downregulation of Igfbp5 mRNA in both hippocampus and cortex. These findings demonstrate significant changes in two important regulatory systems during the sub-acute phase of KA-induced seizures, which ultimately could lead to the development of a number of pathologic processes including neuroinflammation and neuronal death.