Epilepsia
Direct brain stimulation is an emerging treatment of epilepsy. Scheduled or responsive stimulation has been applied. The most explored targets for scheduled stimulation are the anterior nucleus of the thalamus and the hippocampus. The anterior nucleus of the thalamus was studied in a large multicenter trial. There was a significant seizure reduction with the stimulator “on” versus “off” during several...
Even with the latest advancements in antiepileptic drugs (AEDs) there are still many persons whose seizures are not controlled. There are also side effects reported associated with the AEDs. Electrical stimulation of the brain has shown promise toward controlling seizures. However, most brain stimulation techniques involve invasive procedures to implant electrodes and electronic stimulators. There...
Strategies that are efficacious for preventing or treating of epilepsy have been extensively used. This review discusses the positive effects of physical exercise program in experimental models of epilepsy, and considerations of the potential application of physical exercise strategy for preventing or treating temporal lobe epilepsy (TLE) are highlighted. Findings from animal studies indicate that...
Status epilepticus in the immature brain induces neuronal injury in the hippocampal formation, but the mode and mechanism of death are poorly understood. Our laboratory has recently investigated the role of caspase‐3, ‐8, and ‐9 in neuronal injury, using a lithium–pilocarpine model of status epilepticus in 2‐week‐old rat pups. Our results showed that dying neurons in the dentate gyrus and CA1‐subiculum...
Extracellular matrix (ECM) in the brain is composed of molecules synthesized and secreted by neurons and glial cells, which form stable aggregates of diverse composition in the extracellular space. In the mature brain, ECM undergoes a slow turnover and restrains structural plasticity while supporting multiple physiologic processes, including perisomatic γ‐aminobutyric acid (GABA)ergic inhibition,...
Infantile spasms are the classical seizure type of West syndrome. Infantile spasms often herald a dismal prognosis, due to the high probability to evolve into intractable forms of epilepsies with significant cognitive deficits, especially if not adequately treated. The current therapies—high doses of adrenocorticotropic hormone, steroids, or the γ‐aminobutyric acid (GABA) transaminase inhibitor vigabatrin—are...
Antagonists of group I of metabotropic glutamate receptors (mGluRs) exhibit anticonvulsant as well as anxiolytic action in adult rodents. Therefore, we started to study these effects in developing rats. Motor seizures induced by pentylenetetrazol (PTZ) and cortical epileptic afterdischarges (CxADs) elicited by electrical stimulation were used in immature rats. High doses of antagonists were needed...
Antiepileptic drugs (AEDs) such as phenobarbital, phenytoin, and valproic acid, when given in therapeutic doses to neonatal rats, cause pronounced neuronal apoptotic cell death. This effect is especially pronounced in the striatum and cortex during the second postnatal week, a period corresponding to the “brain growth spurt” (third trimester of gestation and early infancy) in humans. Of particular...
Prevention of epileptogenesis is an unmet need in medicine. During the last 3 years, however, several preclinical studies have demonstrated remarkable favorable effects of novel treatments on genetic and acquired epileptogenesis. These include the use of immunosuppressants and treatments that modify cellular adhesion, proliferation, and/or plasticity. In addition, the use of antiepileptic drugs in...
Exposure to the group I metabotropic glutamate receptor (mGluR) agonist dihydroxy phenylglycine (DHPG) induces epileptiform activity in the CA3 region of the hippocampus that persists following washout of DHPG. DHPG also can cause long‐term depression of synaptic transmission, and at some synapses this may be mediated by endocannabinoids. We evaluated whether the selective cannabinoid type 1 (CB1)...
We showed previously that electrographic seizures involving dentate granule cells in organotypic hippocampal slice cultures were dramatically reduced following chronic treatment with the NR2B‐selective antagonist, Ro25,6981, but were increased following chronic treatment with the high‐affinity competitive antagonist, D(‐)‐2‐amino‐5‐phosphonopentanoic acid (D‐APV). To begin to investigate the potential...
Most of the γ‐aminobutyric acid (GABA)ergic interneurons in the cerebral cortex originate from restricted regions of the ventral telencephalon known as the caudal and medial ganglionic eminence (MGE) and from the preoptic area. It is well established that dysfunction of GABAergic interneurons can lead to epilepsy. During the last decade new approaches to prevent, reduce, or reverse the epileptic condition...
We have shown that the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is the kinase involved in the endogenous phosphorylation of the α1 subunit of the γ‐aminobutyric acid (GABA)A receptor (GABAAR), maintaining GABAA‐R function. GABAAR endogenous phosphorylation is opposed by one or several atypical phosphatases. We have shown in addition, using cerebral tissue obtained during...
We used the method of rapid hippocampal kindling to assess the potential antiepileptogenic efficacy of a number of anticonvulsant medications. This method afforded a higher throughput than methods based on traditional kindling or post–status epilepticus models of epileptogenesis. This “compressed epileptogenesis” model also permitted the study of age‐dependent pharmacologic targets, and distinguished...
Neurotrophic factors are involved in the survival of neurons as well as in the proliferation and differentiation of neuronal precursors. Therefore, modulating their levels in lesion areas may exert favorable effects on seizure‐induced damage. However, it is unclear if damage limitation or repair may prevent epileptogenesis; it is also uncertain which neurotrophic factor should be administered for...
Convulsive status epilepticus (CSE) is the most common medical neurologic emergency in childhood. It is associated with significant mortality and morbidity. The estimates for the frequencies of adverse outcomes have a very wide range, but even the lower estimates are clinically important. The major predictor of outcomes following CSE is etiology. The characteristics of the episode of CSE itself, for...
Epilepsy and antiepileptic drugs (AEDs) affect hormones and neuroendocrine systems, which may result in a change in the seizure threshold (catamenial epilepsy) or in comorbidities including sexual dysfunction, reproductive dysfunction, and abnormalities in bone health. Catamenial epilepsy occurs commonly in women with epilepsy. The most commonly reported and studied mechanism proposed to explain why...
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,...
Clinically available anticonvulsant drugs fail to control seizures in approximately 30% of epileptic patients. If hippocampal sclerosis is combined with focal dysplasia or similar developmental alterations, the likelihood of incomplete seizure control may reach >90%. Because only a minority of epilepsy patients benefit from epilepsy surgery, we need more research into the mechanisms of drug refractoriness...