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Infantile spasms (IS) is a devastating epilepsy syndrome of childhood. IS occurs in 3–12‐month‐old infants and is characterized by spasms, interictal electroencephalography (EEG) hypsarrhythmia, and profound mental retardation. Hormonal therapy [adrenocorticotropic hormone (ACTH), corticosteroids] is frequently used, but its efficacy is tainted by severe side effects. For research of novel therapies,...
Inflammatory signaling in the central nervous system (CNS) has been shown to exacerbate both seizure activity and seizure‐induced neuronal injury. However, it has not been firmly established whether neurodegeneration is a prerequisite of proconvulsant effect of neuroinflammation, or whether the latter may facilitate seizures without involving neuronal injury. We examined effects of inflammation in...
Purpose: To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells.
Methods: Fifty‐six female prepubertal Wistar rats (21–24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for...
Purpose: Absence epilepsy may be severe and is frequently accompanied by cognitive delay, yet its metabolic/hemodynamic aspects have not been established. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an isomorphic, predictive, and homologous model of human absence epilepsy. We studied hemodynamic changes related to generalized spike‐and‐wave discharges (GSWDs) in GAERS by using a...
Purpose: In a recent large‐scale gene‐expression study in a rat model of temporal lobe epilepsy (TLE) a persistent up‐regulation in the expression of the SCN7A gene was revealed. The SCN7A gene encodes an atypical sodium channel (Nax), which is involved in osmoregulation via a sensing mechanism for the extracellular sodium concentration. Herein we investigated the expression and cellular distribution...
The ketogenic diet (KD) is an effective treatment for epilepsy, but its mechanisms of action are poorly understood. We investigated the hypothesis that the KD inhibits mammalian target of rapamycin (mTOR) pathway signaling. The expression of pS6 and pAkt, markers of mTOR pathway activation, was reduced in hippocampus and liver of rats fed KD. In the kainate model of epilepsy, KD blocked the hippocampal...
Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile...
Purpose: Adenosine kinase (ADK) represents the key metabolic enzyme for the regulation of extracellular adenosine levels in the brain. In adult brain, ADK is primarily present in astrocytes. Several lines of experimental evidence support a critical role of ADK in different types of brain injury associated with astrogliosis, which is also a prominent morphologic feature of temporal lobe epilepsy (TLE)...
Purpose: Statins are selective inhibitors of 3‐hydroxyl‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase, the rate‐limiting enzyme of the mevalonate pathway for cholesterol biosynthesis. Increasing evidence indicates that statins, particularly atorvastatin, are neuroprotective in several conditions, including stroke, cerebral ischemia, traumatic brain injury, and excitotoxic amino acid exposure....
We previously reported that blood–brain barrier (BBB) disruption was associated with a pathologic angiogenesis in patients with intractable temporal lobe epilepsy (TLE) and in vivo models. This was confirmed by the overexpression of vascular endothelial growth factor (VEGF) in neurons and astrocytes and of its receptor vascular endothelial growth factor‐2 (VEGF‐R2) (or flk1) in endothelial cells....
Purpose: The mammalian target of rapamycin (mTOR) pathway has been implicated in contributing to progressive epileptogenesis in models of chronic epilepsy. Conversely, seizures themselves may directly cause acute activation of the mTOR pathway. To isolate the direct effects of seizures on the mTOR pathway, the time course and mechanisms of mTOR activation were investigated with acute seizures induced...
Postictal refractoriness checked by paired stimulations of the limbic structures was demonstrated to fail in rats <2 weeks old. Cortical epileptic afterdischarges were used in our study to examine if this phenomenon is restricted to old cortical structures or if it is a general one. Rats 12, 15, 18, 25, and 90 days old with implanted electrodes formed the experimental groups. Stimulation was performed...
ObjectiveBrivaracetam (BRV) is a new antiepileptic drug candidate rationally designed for high affinity and selectivity for the synaptic vesicle protein 2A. This study explored anti‐ictogenic and antiepileptogenic effects of BRV in rats at different stages of development.
MethodsUsing a rapid kindling model in P14, P21, P28, and P60 rats, we studied two doses of BRV: 10 and 100 mg/kg injected intraperitoneally...
ObjectiveDeep‐brain electrical stimulation (DBS) is a treatment modality being explored for many neurologic diseases and is a potentially potent means of disrupting the aberrant rhythms that arise during the epileptic seizures that afflict >1% of the population. However, current DBS protocols typically employed are formulated a priori and do not reflect the electrophysiologic dynamics within the...
Objective
Nonadherence to prescribed dosing regimens is a significant problem in the treatment of pediatric and adult chronic epilepsy, and can result in severe consequences to patient outcomes. In this first‐of‐kind preclinical study, the impact of nonadherence on seizure control was studied by simulating human patterns of nonadherence in an animal epilepsy model.
Methods
In study 1, three different...
Objective
Perampanel (PER) is a selective noncompetitive antagonist at α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors, the first of its class approved for the adjunctive treatment of partial onset seizures and generalized seizures. This study explored anti‐ictogenic and antiepileptogenic effects of PER in rats at different stages of development.
Methods
Using a rapid kindling model...
Objective
Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting poor adherence and failures in patient adherence can result in unwarranted alterations to a patient's drug regimen. We have modeled nonadherent patients in an animal model of epilepsy to study how alterations to pharmacotherapy, made without consideration of a patient's adherence, result...
Objective
Inhibition of the mammalian target of rapamycin (mTOR) pathway could be antiepileptogenic in temporal lobe epilepsy (TLE), possibly via anti‐inflammatory actions. We studied effects of the mTOR inhibitor rapamycin and the anti‐inflammatory compound curcumin—also reported to inhibit the mTOR pathway—on epileptogenesis and inflammation in an in vitro organotypic hippocampal‐entorhinal cortex...
Objective
Deep brain stimulation (DBS) is an increasingly applied treatment for various neuropsychiatric disorders including drug‐resistant epilepsy, and it may be optimized by rationalizing the stimulation protocol based on increased knowledge of its mechanism of action. We evaluated the effects of minutes to hours of hippocampal DBS on hippocampal evoked potentials (EPs) and local field potentials...
Objective
Traumatic brain injury (TBI) may lead to the disruption of the intestinal barrier (IB), and to the escape of products of commensal gut bacteria, including lipopolysaccharide (LPS), into the bloodstream. We examined whether lateral fluid percussion injury (LFPI) and post‐traumatic epilepsy (PTE) are associated with the increased intestinal permeability and endotoxemia, and whether these...
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