Investigation of neuroinflammatory response in the acute phase of status epilepticus: effect of mimetic peptide of Annexin A1

• Grant number: 16/04714-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2016
• Effective date (End): August 31, 2018
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: José Victor dos Passos Pinotti
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Clinical and experimental evidences indicate that the inflammatory process in the brain is a crucial mechanism in the physiopathology of epileptic seizures and epilepsy, arousing interest in the use of anti-inflammatory drugs. In this aspect, the mimetic peptide Ac2-26 of the anti-inflammatory protein annexin A1 (ANXA1) represents an interesting target in the regulation of neuroinflammation because of its action in controlling leukocyte transmigration and release of proinflammatory mediators. Thus, we will investigate the role of pharmacological treatment with Ac2-26 peptide in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats. The experimental procedures were approved by the Animal Research Ethics Committee of UNIFESP (CEUA Protocol nº2958050814). Four experimental groups (n = 5 animals/group) will be evaluated: NAÏVE; SHAM; SE (status epilepticus) and SE+Ac2-26 (treated with 1 mg/kg of Ac2-26 after 2, 8 and 14 hours of SE induction). Under these conditions, we will analyze: I) dorsal posterior hippocampus histology and quantification of normal and degenerating neurons; II) identification and quantification of microglia and astrocytes in the hippocampus through immunohistochemistry. The investigation will contribute to a better understanding of the mechanisms involving the action of the Ac2-26 peptide in neuroinflammation and in the discovery of potential therapeutic targets in the epilepsy.