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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Treatment with CCR2 antagonist is neuroprotective but does not alter epileptogenesis in the pilocarpine rat model of epilepsy

Texto completo
Autor(es):
Foresti, Maira Licia [1] ; Arisi, Gabriel Maisonnave [1] ; Campbell, James J. [2] ; Mello, Luiz E. [1, 3]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Physiol Dept, Rua Pedro Toledo 669, L3A, BR-04039032 Sao Paulo, SP - Brazil
[2] ChemoCentryx Inc, Biol, 850 Maude Ave, Mountain View, CA 94043 - USA
[3] Inst DOr Pesquisa & Ensino, Rua Diniz Cordeiro 30, BR-22281100 Botafogo, RJ - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Epilepsy & Behavior; v. 102, JAN 2020.
Citações Web of Science: 0
Resumo

Neuroinflammation role on epileptogenesis has been the subject of increasing interest. Many studies showed elevation in cytokines and chemokines expression following seizures, such as, CCL2 protein (C-C motif ligand 2 chemokine) and its specific receptor, CCR2. In addition, recent studies manipulating the CCL2/CCR2 complex verified improved seizure outcome in different seizure models. In the present study, the effects of CCR2 antagonist was investigated using the pilocarpine rat model of epilepsy. Status epilepticus (SE) was induced by pilocarpine i. p. injection in adult rats. Daily oral treatment with CCR2 antagonist or vehicle was initiated 5 h following SE and lasted 5 or 10 days. Rats were euthanized 5 days after SE to evaluate neuronal damage and glial density or 30 days after SE to investigate spontaneous seizures development and seizure susceptibility to a second hit pentylenetetrazol (PTZ) test. Rats that received CCR2 antagonist presented less degenerating cells at hippocampal CA1 region. There was also a significant decrease in CA1 volume after SE that was not observed in treated rats. On the other hand, microglia cell density increased after SE regardless of CCR2 antagonist use. Treatment with CCR2 antagonist did not alter spontaneous seizure occurrence or later seizure susceptibility to PTZ in chronic rats. Additional rats were pretreated with CCR2 antagonist prior to SE induction, but this did not change SE progression. The data show that oral treatment with CCR2 antagonist is neuroprotective, but does not alter other epileptogenic factors, such as, neuroinflammation, or seizure development, after pilocarpine-induced SE in rats. (C) 2019 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 16/08969-9 - Manipulação farmacológica da interação CCL2/CCR2 na gênese e desenvolvimento da epilepsia do lobo temporal
Beneficiário:Luiz Eugenio Araujo de Moraes Mello
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/11119-4 - Manipulação farmacológica da interação CCL2/CCR2 na gênese e desenvolvimento da epilepsia do lobo temporal
Beneficiário:Maira Licia Foresti
Linha de fomento: Bolsas no Brasil - Pós-Doutorado