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

Background The 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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of neuroinflammation 2019-02, Vol.16 (1), p.32-32, Article 32
Hauptverfasser: Gimenes, Alexandre D, Andrade, Bruna F. D, Pinotti, José Victor P, Oliani, Sonia M, Galvis-Alonso, Orfa Y, Gil, Cristiane D
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Background The 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 Ac.sub.2-26 in an experimental model of status epilepticus (SE) was evaluated. Methods Male Wistar rats were divided into Naive, Sham, SE and SE+Ac.sub.2-26 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 Ac.sub.2-26 (1 mg/kg) were administered intraperitoneally (i.p.) after 2, 8 and 14 h of SE induction. Finally, 24 h after the experiment-onset, rats were euthanized for analyses of neuronal lesion and inflammation. Results Pilocarpine induced generalised SE in all animals, causing neuronal damage, and systemic treatment with Ac.sub.2-26 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. Ac.sub.2-26 reduced the astrocyte marker (glial fibrillary acidic protein; GFAP) levels, as well as interleukin-1[beta] (IL-1[beta]), 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 Ac.sub.2-26, and the phosphorylated extracellular signal-regulated kinase (ERK) in the hippocampal neurons. Conclusions The data suggest a neuroprotective effect of Ac.sub.2-26 in the epileptogenic processes through downregulation of inflammatory mediators and neuronal loss. Keywords: Cytokines, ERK, Fpr2, Glia, Hippocampus, Neuroinflammation
ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-019-1414-7