Evaluation of the maraviroc neuroprotective effects in migraine

• Grant number: 23/01835-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2024
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Luiz Eduardo Nunes Ferreira
• Grantee: Luiz Eduardo Nunes Ferreira
• Host Institution: Universidade Universus Veritas Guarulhos (Univeritas UNG). Guarulhos , SP, Brazil
• Associated researchers: Giselle Fazzioni Passos ; Janaina de Cássia Orlandi Sardi ; José Roberto Santin ; Josué de Moraes ; Juliana Geremias Chichorro
• Associated scholarship(s): 24/16164-7 - In vitro evaluation of maraviroc in CGRP-stimulated neurogenic inflammation in microglia cells, BP.IC

Abstract

Migraine is a complex and quite frequent neurological disorder, without a fully elucidated pathophysiological mechanism. This condition involves trigeminovascular system activation, neuropeptide release, neuroinflammation and vasodilation. Drug repositioning is an efficient strategy in order to expand the pharmacological arsenal. Thus, maraviroc, a CCR5 receptor antagonist, emerges as a candidate due to its peripheral and central anti-inflammatory properties, with promising results in neuroinflammatory disorders. This project aims to evaluate the effectiveness of maraviroc in a migraine model in rats, developed by our group, and to test the neuroprotective potential of the drug in vitro. In vitro, glial (BV-2) cells will be treated (maraviroc) and stimulated (CGRP). Cell viability will be assessed by MTT, nitric oxide and the release of ²-chemokines (MIP-1±, MIP-1² e RANTES) will be quantified. Microglia polarization and the CCR5 expression will be evaluated. The experiments will also be performed in a standardized primary culture of the trigeminal ganglion model. In vivo, CGRP will be inject in the trigeminal ganglion (TG) to induce mechanical periorbital allodynia and the maraviroc effect will be evaluated. The TG will be collected and leukocyte migration will be evaluated. The results will contribute to the understanding of neuroinflammation in migraine, in addition to exploring the potential of maraviroc for an innovative therapeutic approach. (AU)