The Metabolic Profile of Plasma During Epileptogenesis in a Rat Model of Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) arises mostly because of an initial injury. Certain stimuli can make a normal brain prone to repeated, spontaneous seizures via a process called epileptogenesis. This study examined the plasma metabolomics profile in rats with the induced TLE to identify feasible biomarkers that can distinguish progression of epileptogenesis in three different time points and reveal the underlying mechanisms of epileptogenesis. Status epilepticus (SE) was induced by repetitive intraperitoneal injections of low-dose lithium chloride-pilocarpine hydrocholoride. Blood samples were collected 48 h, 1 week, and 6 weeks after SE, respectively. Plasma metabolites were analyzed by nuclear magnetic resonance (NMR) spectrometry. Statistical analysis was performed using MetaboAnalyst 6.0. An orthogonal partial least squares discriminant analysis (OPLS-DA) model was employed to represent variations between the TLE model groups and respective controls. 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. 48 h after SE, dimethyl sulfone (DMSO2) and creatinine levels were decreased, whereas glycine and creatine levels were increased. The only metabolite that changed 1 week after SE was pyruvic acid, which was increased compared to its control level. Lactic acid, pyruvic acid, and succinic acid levels were increased 6 weeks after SE. The identified metabolites were especially related to the tricarboxylic acid cycle and glycine, serine, and threonine metabolism. The results illustrate that distinct plasma metabolites can function as phase-specific biomarkers in TLE and reveal new insights into the mechanisms underlying SE.