title: Lacosamide treatment following status epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical status epilepticus model.
abstract: OBJECTIVE
  The antiepileptic drug, lacosamide, exerts its therapeutic activity by enhancing slow inactivation of voltage-gated sodium channels. Because putative preventive or disease-modifying effects of drugs may affect epileptogenesis, intrinsic severity, and comorbidities, it is of particular interest to assess the effect of lacosamide on the development of epilepsy and associated cellular alterations.
  
  
  METHODS
  The effect of lacosamide was evaluated in an electrical rat status epilepticus (SE) model with a 24-day treatment phase following induction of SE. The impact of lacosamide on the development of spontaneous seizures based on continuous video-electroencephalography (EEG) monitoring, as well as the impact on neuronal cell loss and alterations in hippocampal neurogenesis, was assessed.
  
  
  RESULTS
  Neither low-dose nor high-dose lacosamide affected the development of spontaneous seizures. A dose-dependent neuroprotective effect of lacosamide with significant reduction of neuronal cell loss was observed in the hippocampal CA1 region, as well as in the piriform cortex. In addition, lacosamide attenuated the impact of SE on the rate of hippocampal cell neurogenesis. Moreover, lacosamide prevented a significant rise in the number of persistent basal dendrites.
  
  
  CONCLUSIONS
  Our data do not support an antiepileptogenic effect of lacosamide. However, because lacosamide reduced SE-associated cellular alterations, it would be of interest to determine whether these effects indicate a putative disease-modifying effect of lacosamide in future studies.
authors.affiliation: Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilian-University, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Licko
authors.forename: Natalie
authors.initials: N
authors.lastname: Seeger
authors.forename: Christina
authors.initials: C
authors.lastname: Zellinger
authors.forename: Vera
authors.initials: V
authors.lastname: Russmann
authors.forename: Alain
authors.initials: A
authors.lastname: Matagne
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D004558:Electric Stimulation / Q000009:adverse effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D058953:Neural Stem Cells / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine
keywords: Antiepileptic drug; Epilepsy; Hippocampus; Lacosamide; Neuroprotection; Sodium channel