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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced status epilepticus model: anti-inflammatory and neuroprotective effects

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Author(s):
Gimenes, Alexandre D. [1] ; Andrade, Bruna F. D. [2] ; Pinotti, Jose Victor P. [1] ; Oliani, Sonia M. [1, 3] ; Galvis-Alonso, Orfa Y. [2] ; Gil, Cristiane D. [1, 3]
Total Authors: 6
Affiliation:
[1] Fed Univ Sao Paulo UNIFESP, Dept Morphol & Genet, BR-04023900 Sao Paulo, SP - Brazil
[2] Sao Jose do Rio Preto Sch Med FAMERP, Dept Mol Biol, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil
[3] Sao Paulo State Univ IBILCE UNESP, Inst Biociencias Letras & Ciencias Exatas, Postgrad Biosci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF NEUROINFLAMMATION; v. 16, FEB 12 2019.
Web of Science Citations: 1
Abstract

BackgroundThe inflammatory process has been described as a crucial mechanism in the pathophysiology of temporal lobe epilepsy. The anti-inflammatory protein annexin A1 (ANXA1) represents an interesting target in the regulation of neuroinflammation through the inhibition of leukocyte transmigration and the release of proinflammatory mediators. In this study, the role of the ANXA1-derived peptide Ac2-26 in an experimental model of status epilepticus (SE) was evaluated.MethodsMale Wistar rats were divided into Naive, Sham, SE and SE+Ac2-26 groups, and SE was induced by intrahippocampal injection of pilocarpine. In Sham animals, saline was applied into the hippocampus, and Naive rats were only handled. Three doses of Ac2-26 (1mg/kg) were administered intraperitoneally (i.p.) after 2, 8 and 14h of SE induction. Finally, 24h after the experiment-onset, rats were euthanized for analyses of neuronal lesion and inflammation.ResultsPilocarpine induced generalised SE in all animals, causing neuronal damage, and systemic treatment with Ac2-26 decreased neuronal degeneration and albumin levels in the hippocampus. Also, both SE groups showed an intense influx of microglia, which was corroborated by high levels of ionised calcium binding adaptor molecule 1(Iba-1) and monocyte chemoattractant protein-1 (MCP-1) in the hippocampus. Ac2-26 reduced the astrocyte marker (glial fibrillary acidic protein; GFAP) levels, as well as interleukin-1 (IL-1), interleukin-6 (IL-6) and growth-regulated alpha protein (GRO/KC). These effects of the peptide were associated with the modulation of the levels of formyl peptide receptor 2, a G-protein-coupled receptor that binds to Ac2-26, and the phosphorylated extracellular signal-regulated kinase (ERK) in the hippocampal neurons.ConclusionsThe data suggest a neuroprotective effect of Ac2-26 in the epileptogenic processes through downregulation of inflammatory mediators and neuronal loss. (AU)

FAPESP's process: 16/02012-4 - Evaluation of the immunomodulatory activity of annexin A1 protein in the regulation of inflammatory disorders of the gastrointestinal system: studies in vivo and in vitro experimental models
Grantee:Sonia Maria Oliani
Support Opportunities: Regular Research Grants
FAPESP's process: 17/26872-5 - Study of anti-inflammatory and proinflammatory proteins as possible therapeutic targets in experimental models of neuroinflammation and cutaneous inflammation
Grantee:Cristiane Damas Gil
Support Opportunities: Regular Research Grants