Modification of the natural progression of epileptogenesis by means of biperiden in the pilocarpine model of epilepsy

Modification of the natural progression of epileptogenesis by means of biperiden in the pilocarpine model of epilepsy

Author Bittencourt, Simone Autor UNIFESP Google Scholar
Ferrazoli, Eneas Autor UNIFESP Google Scholar
Valente, Maria Fernanda Autor UNIFESP Google Scholar
Romariz, Simone Autor UNIFESP Google Scholar
Janisset, Nilma R. L. L. Autor UNIFESP Google Scholar
Macedo, Carlos Eduardo Autor UNIFESP Google Scholar
Antonio, Bruno de Brito Autor UNIFESP Google Scholar
Barros, Vanessa Autor UNIFESP Google Scholar
Mundim, Mayara Autor UNIFESP Google Scholar
Porcionatto, Marimelia Autor UNIFESP Google Scholar
Aarão, Mayra Consuelo Google Scholar
Miranda, Maisa Ferreira Google Scholar
Rodrigues, Antonio Marcio Google Scholar
Guimaraes de Almeida, Antonio-Carlos Google Scholar
Longo, Beatriz M. Autor UNIFESP Google Scholar
Mello, Luiz E. Autor UNIFESP Google Scholar
Abstract Brain injuries are often associated with the later development of epilepsy. Evidence suggests that morphological and functional changes occur in the remaining neural tissue during a silent (or latent) period in which no seizures are expressed. It is believed that this silent (reorganization) period may provide a therapeutic window for modifying the natural history of disease progression. Here we provide evidence that biperiden, a muscarinic anticholinergic agent, is able to alter disease progression in an animal model of epilepsy. We observed that biperiden was capable of slowing the manifestation of the first spontaneous epileptic seizure and effectively reduced the severity and number of recurrent, spontaneous epileptic seizures during the animals' lifespan. Biomolecular (microdialysis) and electrophysiological (extracellular field recordings) studies determined that biperiden was capable of elevating the threshold of hippocampal excitability, thereby making the hippocampal glutamatergic pathways less responsive to stimuli when high concentrations of potassium were used in vivo or in vitro. Notably, there was no hindrance of long-term memory or learning (a potential problem given the amnestic nature of biperiden). We conclude that biperiden has antiepileptogenic potential and may represent an opportunity for the prevention of post-traumatic epilepsy.
Keywords Disease modifying agents
Anti-epileptogenesis
Symptomatic epilepsies
Neuronal plasticity
Anticholinergic drugs
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor CNPq
CAPES
FAPEMIG
FAPESP/CInAPCe
Date 2017
Published in Epilepsy Research. Amsterdam, v. 138, p. 88-97, 2017.
ISSN 0920-1211 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 88-97
Origin http://dx.doi.org/10.1016/j.eplepsyres.2017.10.019
Access rights Closed access
Type Article
Web of Science ID WOS:000418216900013
URI https://repositorio.unifesp.br/handle/11600/58076

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