Propylparaben applied after pilocarpine-induced status epilepticus modifies hippocampal excitability and glutamate release in rats.
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.
Department of Pharmacobiology, Center for Research and Advanced Studies (CINVESTAV), Mexico City, Mexico.
César Emmanuel
CE
Santana-Gómez
Unit for Medical Research in Neurological Diseases, Specialties Hospital, National Medical Center SXXI (CMN-SXXI), Mexico City, Mexico.
Sandra Adela
SA
Orozco-Suárez
Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, Buenos Aires, Argentina.
Alan
A
Talevi
Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, Buenos Aires, Argentina.
Luis
L
Bruno-Blanch
Department of Neuroscience Research, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico.
Víctor Manuel
VM
Magdaleno-Madrigal
Department of Neuroscience Research, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico.
Rodrigo
R
Fernández-Mas
Department of Pharmacobiology, Center for Research and Advanced Studies (CINVESTAV), Mexico City, Mexico. Electronic address: lrocha@cinvestav.mx.
Luisa
L
Rocha
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002452:Cell Count; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005452:Fluoresceins / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity; D010226:Parabens / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000927:Anticonvulsants; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D018721:Muscarinic Agonists; D010226:Parabens; C435731:fluoro jade; D010862:Pilocarpine; D018698:Glutamic Acid; D010751:Phosphopyruvate Hydratase; D003975:Diazepam; C006068:propylparaben
Cell damage; Electrographic activity; Glutamate; Neuronal excitability; Neuroprotection