1. Academic Validation
  2. 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

  • Epilepsy Res. 2017 Dec;138:88-97. doi: 10.1016/j.eplepsyres.2017.10.019.
Simone Bittencourt 1 Enéas Ferrazoli 1 Maria Fernanda Valente 1 Simone Romariz 1 Nilma R L L Janisset 1 Carlos Eduardo Macedo 1 Bruno de Brito Antonio 2 Vanessa Barros 1 Mayara Mundim 3 Marimélia Porcionatto 3 Mayra Consuelo Aarão 4 Maísa Ferreira Miranda 4 Antônio Márcio Rodrigues 4 Antônio-Carlos Guimarães de Almeida 4 Beatriz M Longo 1 Luiz E Mello 5
Affiliations

Affiliations

  • 1 Departament of Physiology, Universidade Federal de São Paulo, São Paulo, SP 04039-032, Brazil.
  • 2 Departament of Psychobiology, Universidade Federal de São Paulo, São Paulo/SP 04039-032, Brazil.
  • 3 Department of Biochemistry, Universidade Federal de São Paulo, São Paulo/SP 04039-032, Brazil.
  • 4 Departament of Biosystems Engineering, Universidade Federal de São João Del Rei, Minas Gerais, MG 36307-352, Brazil.
  • 5 Departament of Physiology, Universidade Federal de São Paulo, São Paulo, SP 04039-032, Brazil. Electronic address: lemello@unifesp.br.
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

Anti-epileptogenesis; Anticholinergic drugs; Disease modifying agents; Neuronal plasticity; Symptomatic epilepsies.

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