Alterations of specific metabolites during epileptogenesis in plasma of rats with lithium-pilocarpine-induced temporal lobe epilepsy

Temporal lobe epilepsy (TLE) arises mostly due to an initial injury. Certain stimuli can make a normal brain prone to repeated, spontaneous seizures via a process called epileptogenesis. The aim of this study is to examine the plasma metabolomics profile in TLE-induced rats to find feasible biomarkers that can distinguish phases of epileptogenesis. Status epilepticus (SE) was induced by low-dose-repetitive-lithium chloride–pilocarpine hydrocholoride intraperitoneal injections. Control groups just received saline injections. Blood samples were collected 48 hours, 7 days and 6 weeks after SE, representing acute, latent and chronic phases, respectively. The plasma was isolated by cold-centrifugation. The metabolites were analyzed by nuclear magnetic resonance (NMR) spectrometry. Statistical analysis was performed and presented by using Metaboanalyst 5.0. The data underwent logarithmic transformation using base 10 and were automatically scaled to achieve normalization. Volcano plot analysis was used to identify key features, applying a fold-change criterion of 1.5 and a t-test threshold of 0.05. An OPLS-DA model was employed to represent variations between TLE model groups and respective controls. The results were shown in Table 1. Dimethylsulfone and creatinine were decreased in the acute phase, while glycine and creatine were increased. The only metabolite that changed in the latent phase was pyruvic acid, which was increased compared to the control rats. Lactic acid, pyruvic acid and succinic acid were increased in the chronic phase. These findings indicate that distinct plasma metabolites may function as phase-specific biomarkers in TLE, providing insights into the biochemical changes during epileptogenesis.