Cortical low‐frequency power correlates with behavioral impairment in animal model of focal limbic seizures

Abstract

Objective

Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a “network inhibition” phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures.

Methods

Focal onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response ...

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Epileptic heart: A clinical syndromic approach

Abstract

Prevention of premature death in patients with chronic epilepsy remains a major challenge. Multiple pathophysiologic factors have been implicated, with intense investigation of cardiorespiratory mechanisms. Up to four in five patients with chronic epilepsy exhibit cardiovascular comorbidities. These findings led us to propose the concept of an “epileptic heart,” defined as “a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction.” Among the most prominent ...

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Ketogenic diet–mediated seizure reduction preserves CA1 cell numbers in epileptic Kcna1‐null mice: An unbiased stereological assessment

Abstract

There is growing evidence for the disease-modifying potential of metabolic therapies, including the ketogenic diet (KD), which is used to treat medically intractable epilepsy. However, it remains unclear whether the KD exerts direct effects on histopathological changes in epileptic brain, or whether the changes are a consequence of diet-induced reduction in seizure activity. Here, we used unbiased stereological techniques to quantify the seizure-induced reduction in cell number in the CA1 region of the hippocampus of epileptic Kcna1-null mice and compared ...

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Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions

Abstract

Objective

Infantile spasms may evolve into persistent epilepsies including Lennox-Gastaut syndrome. We compared adult epilepsy outcomes in models of infantile spasms due to structural etiology (multiple-hit model) or focal cortical inflammation and determined the anti-epileptogenic effects of pulse-rapamycin, previously shown to stop spasms in multiple-hit rats.

Methods

Spasms were induced in 3-day-old male rats via right intracerebral doxorubicin/lipopolysaccharide (multiple-hit model) infusions. Controls and sham rats were used. Separate multiple-hit rats received pulse-rapamycin or vehicle intraperitoneally between postnatal days 4 and 6. In adult ...

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Early‐life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study

Abstract

Objective

We aimed to evaluate early-life epilepsy incidence, seizure types, severity, risk factors, and treatments among survivors of acute neonatal seizures.

Methods

Neonates with acute symptomatic seizures born 7/2015-3/2018 were prospectively enrolled at nine Neonatal Seizure Registry sites. One-hour EEG was recorded at age three months. Post-neonatal epilepsy and functional development (Warner Initial Developmental Evaluation of Adaptive and Functional Skills – WIDEA-FS) were assessed. Cox regression was used to assess epilepsy-free survival.

Results

Among 282 infants, 37 (13%) had post-neonatal epilepsy by 24-months [median age ...

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Gut metabolite S‐equol ameliorates hyperexcitability in entorhinal cortex neurons following Theiler murine encephalomyelitis virus‐induced acute seizures

Abstract

Objective

A growing body of evidence indicates a potential role for the gut–brain axis as a novel therapeutic target in treating seizures. The present study sought to characterize the gut microbiome in Theiler murine encephalomyelitis virus (TMEV)-induced seizures, and to evaluate the effect of microbial metabolite S-equol on neuronal physiology as well as TMEV-induced neuronal hyperexcitability ex vivo.

Methods

We infected C57BL/6J mice with TMEV and monitored the development of acute behavioral seizures 0–7 days postinfection (dpi). Fecal samples were collected at 5–7 dpi ...

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Carbonic anhydrase inhibitors suppress seizures in a rat model of birth asphyxia

Abstract

Objective

Seizures are common in neonates recovering from birth asphyxia but there is general consensus that current pharmacotherapy is suboptimal and that novel antiseizure drugs are needed. We recently showed in a rat model of birth asphyxia that seizures are triggered by the post-asphyxia recovery of brain pH. Here our aim was to investigate whether carbonic anhydrase inhibitors (CAIs), which induce systemic acidosis, block the post-asphyxia seizures.

Methods

The CAIs acetazolamide (AZA), benzolamide (BZA), and ethoxzolamide (EZA) were administered intraperitoneally or intravenously to ...

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Dietary medium chain triglycerides for management of epilepsy: New data from human, dog, and rodent studies

Abstract

Many studies show that glucose metabolism in epileptic brain areas can be impaired. Energy is crucial to maintain normal brain function, including ion and neurotransmitter balances. Energy deficits can lead to disruption of ion gradients, which can trigger neuronal depolarization and generation of seizures. Thus, perturbed metabolic processing of glucose in epileptogenic brain areas indicates a specific nutritional need for people and animals with epilepsy, as they are likely to benefit from auxiliary brain fuels other than glucose. Ketogenic diets ...

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