ROS/TRPA1/CGRP signaling mediates cortical spreading depression

Liwen Jiang, Dongqing Ma, Blair D. Grubb, Minyan Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Objectives: The transient receptor potential ankyrin A 1 (TRPA1) channel and calcitonin gene-related peptide (CGRP) are targets for migraine prophylaxis. This study aimed to understand their mechanisms in migraine by investigating the role of TRPA1 in cortical spreading depression (CSD) in vivo and exploring how reactive oxygen species (ROS)/TRPA1/CGRP interplay in regulating cortical susceptibility to CSD. Methods: Immunohistochemistry was used for detecting TRPA1 expression. CSD was induced by K + on the cerebral cortex, monitored using electrophysiology in rats, and intrinsic optical imaging in mouse brain slices, respectively. Drugs were perfused into contralateral ventricle of rats. Lipid peroxidation (malondialdehyde, MDA) analysis was used for indicating ROS level. Results: TRPA1 was expressed in cortical neurons and astrocytes of rats and mice. TRPA1 deactivation by an anti-TRPA1 antibody reduced cortical susceptibility to CSD in rats and decreased ipsilateral MDA level induced by CSD. In mouse brain slices, H 2 O 2 facilitated submaximal CSD induction, which disappeared by the antioxidant, tempol and the TRPA1 antagonist, A-967079; Consistently, TRPA1 activation reversed prolonged CSD latency and reduced magnitude by the antioxidant. Further, blockade of CGRP prolonged CSD latency, which was reversed by H 2 O 2 and the TRPA1 agonist, allyl-isothiocyanate, respectively. Conclusions: ROS/TRPA1/CGRP signaling plays a critical role in regulating cortical susceptibility to CSD. Inhibition ROS and deactivation of TRPA1 channels may have therapeutic benefits in preventing stress-triggered migraine via CGRP.

Original languageEnglish
Article number25
JournalJournal of Headache and Pain
Issue number1
Publication statusPublished - 6 Mar 2019


  • Calcitonin gene-related peptide
  • Cortical spreading depression
  • Migraine
  • Reactive oxygen species
  • Transient receptor potential ankyrin a 1


Dive into the research topics of 'ROS/TRPA1/CGRP signaling mediates cortical spreading depression'. Together they form a unique fingerprint.

Cite this