title: Postictal alterations induced by intrahippocampal injection of pilocarpine in C57BL/6 mice.
abstract: Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. The pilocarpine (PILO) experimental model of TLE portrays behavioral and pathophysiological changes in rodents that are very similar to those found in humans with TLE. However, this model is associated with an unfortunate high mortality rate. Studies have shown that intrahippocampal injection of PILO, while having a much smaller mortality rate, induces status epilepticus (SE) that secondarily leads to TLE. To the best of our knowledge, the present study was the first to evaluate the cognitive and histological alterations 72h after intrahippocampal microinjection of PILO in C57BL/6 mice. Seventy percent of mice developed status epilepticus (SE) after PILO administration, and all animals survived after SE. Seventy-two hours after SE, mice presented memory impairment in both Novel Object Recognition (recognition index - vehicle: 67.57±4.46% vs PILO: 52.33±3.29%) and Contextual Fear Conditioning (freezing time - vehicle: 203±20.43 vs PILO: 107.80±25.17s) tasks. Moreover, using Nissl and NeuN staining, we observed in PILO-treated mice a significant decrease in cell viability and an increase in neuronal loss in all three hippocampal regions analyzed, cornus ammonis (CA) 1, CA3, and dentate gyrus (DG), in comparison with the control group. Additionally, using Iba-1 staining, we observed in PILO-treated mice a significant increase in microglial proliferation in CA1, CA3, and DG of the hippocampus. Therefore, intrahippocampal PILO microinjection is an efficient route to induce SE and acute postictal epileptogenic-like alterations in C57BL/6 mice.
authors.affiliation: Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
authors.forename: Isabel Vieira de Assis
authors.initials: IVA
authors.lastname: Lima
authors.affiliation: Department of Pharmacology, Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil.
authors.forename: Alline Cristina de
authors.initials: AC
authors.lastname: Campos
authors.affiliation: Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
authors.forename: Paula Maria Quaglio
authors.initials: PMQ
authors.lastname: Bellozi
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
authors.forename: Juliana Guimaraes
authors.initials: JG
authors.lastname: Doria
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
authors.forename: Fabiola Mara
authors.initials: FM
authors.lastname: Ribeiro
authors.affiliation: Department of Biophysics and Physiology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil. Electronic address: mfdm@icb.ufmg.br.
authors.forename: Marcio Flavio Dutra
authors.initials: MFD
authors.lastname: Moraes
authors.affiliation: Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil. Electronic address: antoniooliveira@icb.ufmg.br.
authors.forename: Antonio Carlos Pinheiro
authors.initials: ACP
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced*; D005911:Gliosis / Q000139:chemically induced*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010862:Pilocarpine / Q000008:administration & dosage / Q000494:pharmacology*; D013226:Status Epilepticus / Q000139:chemically induced*
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine
keywords: Memory; Microglia; Neurodegeneration; Pilocarpine; Temporal lobe epilepsy