Effects of early life seizures on coordination of hippocampal–prefrontal networks: Influence of sex and dynamic brain states

Abstract

Objective

Early life seizures (ELSs) alter activity-dependent maturation of neuronal circuits underlying learning and memory. The pathophysiological mechanisms underpinning seizure-induced cognitive impairment are not fully understood, and critical variables such as sex and dynamic brain states with regard to cognitive outcomes have not been explored. We hypothesized that in comparison to control (CTL) rats, ELS rats would exhibit deficits in spatial cognition correlating with impaired dynamic neural signal coordination between the hippocampus and medial prefrontal cortex (mPFC).

Methods

Male and female rat pups ...

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Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program

Abstract

Objective

Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying a mutation in the SCN1A gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In the clinic, individuals with DS often present first with a febrile seizure and, subsequently, generalized tonic-clonic seizures that can continue throughout life. To facilitate the development of ASDs for DS, the contract site of the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) ...

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Folic acid supplementation rescues valproic acid‐induced developmental neurotoxicity and behavioral alterations in zebrafish embryos

Abstract

Objective

Fetal exposure to the anticonvulsant drug valproic acid (VPA), used to treat certain types of epilepsy, increases the risk for birth defects, including neural tube defects, as well as learning difficulties and behavioral problems. Here, we investigated neurotoxic effects of VPA exposure using zebrafish as a model organism. The capacity of folic acid (FA) supplementation to rescue the VPA-induced neuronal and behavioral perturbations was also examined.

Methods

Zebrafish embryos of different transgenic lines with neuronal green fluorescent protein expression were exposed to ...

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Early onset epilepsy and sudden unexpected death in epilepsy with cardiac arrhythmia in mice carrying the early infantile epileptic encephalopathy 47 gain‐of‐function FHF1(FGF12) missense mutation

Summary

Objective

Fibroblast growth factor homologous factors (FHFs) are brain and cardiac sodium channel‐binding proteins that modulate channel density and inactivation gating. A recurrent de novo gain‐of‐function missense mutation in the FHF1(FGF12) gene (p.Arg52His) is associated with early infantile epileptic encephalopathy 47 (EIEE47; Online Mendelian Inheritance in Man database 617166). To determine whether the FHF1 missense mutation is sufficient to cause EIEE and to establish an animal model for EIEE47, we sought to engineer this mutation into mice.

Methods

The Arg52His mutation was introduced ...

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Supporting treatment adherence regimens in children with epilepsy: A randomized clinical trial

Abstract

Objective

This study was undertaken to examine the efficacy of a family‐tailored education and problem‐solving behavioral intervention, Supporting Treatment Adherence Regimens (STAR), in young children (2–12 years old) with new onset epilepsy compared to an attention control (i.e., education only [EO]) intervention. Participants randomized to the STAR intervention were hypothesized to demonstrate significantly improved adherence at postintervention and 3‐, 6‐, and 12‐month follow‐up visits compared to the EO intervention. Seizure and health‐related quality of life (HRQOL) outcomes were also examined.

Methods

Two hundred children ...

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Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder

Abstract

CDKL5 deficiency disorder (CDD) is an X‐linked pharmacoresistant neurogenetic disorder characterized by global developmental delays and uncontrolled seizures. Fenfluramine (FFA), an antiseizure medication (ASM) indicated for treating convulsive seizures in Dravet syndrome, was assessed in six patients (five female; 83%) with CDD whose seizures had failed 5–12 ASMs or therapies. Median age at enrollment was 6.5 years (range: 2–26 years). Mean FFA treatment duration was 5.3 months (range: 2–9 months) at 0.4 mg/kg/day (n = 2) or 0.7 mg/kg/day (n = 4; maximum: 26 mg/day). One patient had valproate added for ...

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Neural recruitment by ephaptic coupling in epilepsy

Abstract

Objective

One of the challenges in treating patients with drug‐resistant epilepsy is that the mechanisms of seizures are unknown. Most current interventions are based on the assumption that epileptic activity recruits neurons and progresses by synaptic transmission. However, several experimental studies have shown that neural activity in rodent hippocampi can propagate independently of synaptic transmission. Recent studies suggest these waves are self‐propagating by electric field (ephaptic) coupling. In this study, we tested the hypothesis that neural recruitment during seizures can occur ...

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Astrocyte and glutamate involvement in the pathogenesis of epilepsy in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) can increase the risk of epilepsy by up to 10‐fold compared to healthy age‐matched controls. However, the pathological mechanisms that underlie this increased risk are poorly understood. Because disruption in brain glutamate homeostasis has been implicated in both AD and epilepsy, this might play a mechanistic role in the pathogenesis of epilepsy in AD. Prior to the formation of amyloid beta (Aβ) plaques, the brain can undergo pathological changes as a result of increased production of amyloid ...

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The clinical utility of a memory specialization index in epilepsy surgery patients with unilateral hippocampal sclerosis

Abstract

Objective

Although group studies provide some support for the material‐specific model of memory function, there are considerable individual variations in memory function in people with temporal lobe epilepsy, even in those with the same underlying pathology. In this proof‐of‐concept study, we examined the sensitivity and specificity of a single measure of an individual’s relative strength for the encoding of verbal or visual learning.

Methods

Six hundred ninety‐two patients with left hemisphere language dominance and unilateral hippocampal sclerosis completed verbal and visual encoding tasks ...

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A combination of phenobarbital and the bumetanide derivative bumepamine prevents neonatal seizures and subsequent hippocampal neurodegeneration in a rat model of birth asphyxia

Abstract

Objectives

Bumetanide was suggested as an adjunct to phenobarbital for suppression of neonatal seizures. This suggestion was based on the idea that bumetanide, by reducing intraneuronal chloride accumulation through inhibition of the Na‐K‐2Cl cotransporter NKCC1, may attenuate or abolish depolarizing γ‐aminobutyric acid (GABA) responses caused by birth asphyxia. However, a first proof‐of‐concept clinical trial failed. This could have had several reasons, including bumetanide’s poor brain penetration, the wide cellular NKCC1 expression pattern in the brain, and problems with the general concept ...

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