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Antiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including migraine headache, chronic neuropathic pain, mood disorders, schizophrenia and various neuromuscular syndromes. In many of these conditions, as in epilepsy, the drugs act by modifying the excitability of nerve (or muscle) through effects on voltage-gated sodium and(More)
Since its first marketing as an antiepileptic drug (AED) 35 years ago in France, valproate has become established worldwide as one of the most widely used AEDs in the treatment of both generalised and partial seizures in adults and children. The broad spectrum of antiepileptic efficacy of valproate is reflected in preclinical in vivo and in vitro models,(More)
  • Wilko D. Altrock, Susanne tom Dieck, Maxim Sokolov, Alexander C. Meyer, Albrecht Sigler, Cord Brakebusch +16 others
  • 2003
Mutant mice lacking the central region of the presynaptic active zone protein Bassoon were generated to establish the role of this protein in the assembly and function of active zones as sites of synaptic vesicle docking and fusion. Our data show that the loss of Bassoon causes a reduction in normal synaptic transmission, which can be attributed to the(More)
Animal models for seizures and epilepsy have played a fundamental role in advancing our understanding of basic mechanisms underlying ictogenesis and epileptogenesis and have been instrumental in the discovery and preclinical development of novel antiepileptic drugs (AEDs). However, there is growing concern that the efficacy of drug treatment of epilepsy has(More)
PURPOSE Weak direct currents induce lasting alterations of cortical excitability in animals and humans, which are controlled by polarity, duration of stimulation, and current strength applied. To evaluate its anticonvulsant potential, transcranial direct current stimulation (tDCS) was tested in a modified cortical ramp-stimulation model of focal epilepsy.(More)
Many patients with epilepsy suffer from psychiatric comorbidities including depression, anxiety, psychotic disorders, cognitive, and personality changes, but the mechanisms underlying the association between epilepsy and psychopathology are only incompletely understood. Animal models of epilepsy, such as the pilocarpine model of acquired temporal lobe(More)
Accumulating evidence suggests that changes in neuronal chloride homeostasis may be involved in the mechanisms by which brain insults induce the development of epilepsy. A variety of brain insults, including status epilepticus (SE), lead to changes in the expression of the cation-chloride cotransporters KCC2 and NKCC1, resulting in intracellular chloride(More)
For several decades, both in vitro and in vivo models of seizures and epilepsy have been employed to unravel the molecular and cellular mechanisms underlying the occurrence of spontaneous recurrent seizures (SRS)-the defining hallmark of the epileptic brain. However, despite great advances in our understanding of seizure genesis, investigators have yet to(More)
PURPOSE Different adenosine triphosphate (ATP)-driven multidrug transporters have been described to be expressed in the luminal membrane of blood-brain barrier (BBB) endothelial cells. At this site, multidrug transporters have been suggested to restrict penetration of drugs into the brain. Increasing evidence suggests that overexpression of different(More)