Summary: Purpose: Administration of carisbamate during status epilepticus (SE) prevents the occurrence of motor seizures in the lithium–pilocarpine model and leads in a subpopulation of rats to spike‐and‐wave discharges characteristic of absence epilepsy. Widespread neuroprotection accompanied this change in seizure expression. To assess whether these carisbamate‐induced changes affected comorbidity, we used a large battery of behavioral tests in rats that had developed temporal lobe or absence‐like seizures.Methods: Lithium–pilocarpine or saline was administered to 60 adult rats. Carisbamate (90 mg/kg) or diazepam and saline was given 1 h after SE onset, and repeated 8 h later and twice daily over 6 more days. Rats were video‐monitored for 2 months. Subsequently, locomotor activity, anxiety, and various types of memory were assessed.Key Findings: In rats with motor seizures, treated or not with carisbamate, all features of behavior were impaired compared to controls. Rats exhibiting absence‐like seizures after carisbamate treatment behaved as controls in all paradigms tested along with widespread neuroprotection.Significance: Carisbamate treatment leading to absence‐like instead of temporal lobe seizures impressively prevented behavioral comorbidities reported by patients with epilepsy as the most disabling.

Summary: Objective: Temporal lobe epilepsy is a relatively frequent, invalidating, and often refractory neurologic disorder. It is associated with cognitive impairments that affect memory and executive functions. In the rat lithium‐pilocarpine temporal lobe epilepsy model, memory impairment and anxiety disorder are classically reported. Here we evaluated sustained visual attention in this model of epilepsy, a function not frequently explored.Methods: Thirty‐five Sprague‐Dawley rats were subjected to lithium‐pilocarpine status epilepticus. Twenty of them received a carisbamate treatment for 7 days, starting 1 h after status epilepticus onset. Twelve controls received lithium and saline. Five months later, attention was assessed in the five‐choice serial reaction time task, a task that tests visual attention and inhibitory control (impulsivity/compulsivity). Neuronal counting was performed in brain regions of interest to the functions studied (hippocampus, prefrontal cortex, nucleus basalis magnocellularis, and pedunculopontine tegmental nucleus).Results: Lithium‐pilocarpine rats developed motor seizures. When they were able to learn the task, they exhibited attention impairment and a tendency toward impulsivity and compulsivity. These disturbances occurred in the absence of neuronal loss in structures classically related to attentional performance, although they seemed to better correlate with neuronal loss in hippocampus. Globally, rats that received carisbamate and developed motor seizures were as impaired as untreated rats, whereas those that did not develop overt motor seizures performed like controls, despite evidence for hippocampal damage.Significance: This study shows that attention deficits reported by patients with temporal lobe epilepsy can be observed in the lithium‐pilocarpine model. Carisbamate prevents the occurrence of motor seizures, attention impairment, impulsivity, and compulsivity in a subpopulation of neuroprotected rats.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Mesial temporal lobe epilepsy (MTLE) is usually associated with drug-resistant seizures and cognitive deficits. Efforts have been made to improve the understanding of the pathophysiology of MTLE for new therapies. In this study, we used proteomics to determine the differential expression of proteins in the hippocampus of patients with MTLE compared to control samples. By using the two-dimensional electrophoresis method (2-DE), the proteins were separated into spots and analyzed by LC-MS/MS. Spots that had different densitometric values for patients and controls were selected for the study. The following proteins were found to be up-regulated in patients: isoform 1 of serum albumin (ALB), proton ATPase catalytic subunit A (ATP6V1A), heat shock protein 70 (HSP70), dihydropyrimidinase-related protein 2 (DPYSL2), isoform 1 of myelin basic protein (MBP), and dihydrolipoamide S-acethyltransferase (DLAT). The protein isoform 3 of the spectrin alpha chain (SPTAN1) was down-regulated while glutathione S-transferase P (GSTP1) and protein DJ-1 (PARK7) were found only in the hippocampus of patients with MTLE. Interactome analysis of the nine proteins of interest revealed interactions with 20 other proteins, most of them involved with metabolic processes (37%), presenting catalytic activity (37%) and working as hydrolyses (25%), among others. Our results provide evidence supporting a direct link between synaptic plasticity, metabolic disturbance, oxidative stress with mitochondrial damage, the disruption of the blood–brain barrier and changes in CNS structural proteins with cell death and epileptogenesis in MTLE. Besides this, the presence of markers of cell survival indicated a compensatory mechanism. The over-expression of GSTP1 in MTLE could be related to drug-resistance.