Propylparaben applied after pilocarpine-induced status epilepticus modifies hippocampal excitability and glutamate release in rats

Neurotoxicology. 2017 Mar:59:110-120. doi: 10.1016/j.neuro.2017.01.009. Epub 2017 Feb 4.

Abstract

Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na+ channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low-frequency oscillations (0.1-13Hz bands, p<0.001), a reduced potency of 30-250Hz bands (p<0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post-SE period is able to prevent the long-term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity.

Keywords: Cell damage; Electrographic activity; Glutamate; Neuronal excitability; Neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Anticonvulsants / therapeutic use*
  • Cell Count
  • Diazepam / therapeutic use
  • Disease Models, Animal
  • Electric Stimulation
  • Fluoresceins / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Muscarinic Agonists / toxicity
  • Parabens / therapeutic use*
  • Phosphopyruvate Hydratase / metabolism
  • Pilocarpine / toxicity
  • Rats
  • Rats, Wistar
  • Status Epilepticus / chemically induced
  • Status Epilepticus / drug therapy*
  • Status Epilepticus / pathology

Substances

  • Anticonvulsants
  • Fluoresceins
  • Glial Fibrillary Acidic Protein
  • Muscarinic Agonists
  • Parabens
  • fluoro jade
  • Pilocarpine
  • Glutamic Acid
  • Phosphopyruvate Hydratase
  • Diazepam
  • propylparaben