Urinary Metabolic Profiling During Epileptogenesis in Rat Model of Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy.

: Temporal lobe epilepsy (TLE) often develops following an initial brain injury, where specific triggers lead to epileptogenesis-a process transforming a healthy brain into one prone to spontaneous, recurrent seizures. Although electroencephalography (EEG) remains the primary diagnostic tool for epilepsy, it cannot predict the risk of epilepsy after brain injury. This limitation highlights the need for biomarkers, particularly those measurable in peripheral samples, to assess epilepsy risk. This study investigated urinary metabolites in a rat model of TLE to identify biomarkers that track epileptogenesis progression across the acute, latent, and chronic phases and elucidate the underlying mechanisms. : Status epilepticus (SE) was induced in rats using repeated intraperitoneal injections of lithium chloride-pilocarpine hydrochloride. Urine samples were collected 48 h, 1 week, and 6 weeks after SE induction. Nuclear magnetic resonance spectrometry was used for metabolomic analysis, and statistical evaluations were performed using MetaboAnalyst 6.0. Differences between epileptic and control groups were represented using the orthogonal partial least squares discriminant analysis (OPLS-DA) model. Volcano plot analysis identified key metabolic changes, applying a fold-change threshold of 1.5 and a -value < 0.05. : The acute phase exhibited elevated levels of acetic acid, dihydrothymine, thymol, and trimethylamine, whereas glycolysis and tricarboxylic acid cycle metabolites, including pyruvic and citric acids, were reduced. Both the acute and latent phases showed decreased theobromine, taurine, and allantoin levels, with elevated 1-methylhistidine in the latent phase. The chronic phase exhibited reductions in pimelic acid, tiglylglycine, D-lactose, and xanthurenic acid levels. : These findings highlight stage-specific urinary metabolic changes in TLE, suggesting distinct metabolites as biomarkers for epileptogenesis and offering insights into the mechanisms underlying SE progression.