Changes in innate immunity in chronic migraine. Role of Toll-like receptors 2 and 4 as key players in migraine chronification and potential therapeutic targets

  1. Domínguez Vivero, Clara
Supervised by:
  1. Rogelio Leira Muiño Director
  2. José Antonio Castillo Sánchez Director

Defence university: Universidade de Santiago de Compostela

Fecha de defensa: 29 April 2021

Committee:
  1. Julio Pascual Gómez Chair
  2. Xiana Rodríguez Osorio Secretary
  3. Isabel Pavao Martins Committee member
Department:
  1. Department of Psychiatry, Radiology, Public Health, Nursing and Medicine

Type: Thesis

Teseo: 659598 DIALNET lock_openMINERVA editor

Abstract

Migraine is a complex disorder that involves several physiopathological mechanisms. Toll-like receptors (TLRs) are involved in neuroinflammation, but their role in migraine is not completely understood. This translational study investigates whether expression of Toll-like receptors 2 and 4 (TLR2 and TLR4) is increased in chronic migraine (CM) patients, and if TLR4 is involved in the vascular response to CSD. With this aim, we designed a clinical cross-sectional study measuring peripheral blood expression of TLR2 and TLR4 and a experimental study based on an animal model of cortical spreading depolarization (CSD). CM patients showed increased expression of TLR4 and TLR2 in peripheral blood. TLR4 KO mice had a different response to CSD stimulation that was reproduced after pharmacological blockade of TLR4. Our results suggest that TLR2 and TLR4 may have a role in migraine pathophysiology, providing a potential novel strategy for treatment.