Related Experiment Video
Updated: Jan 28, 2026

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro
Published on: June 13, 2011
ROS/TRPA1/CGRP signaling mediates cortical spreading depression
Liwen Jiang1,2,3, Dongqing Ma1,2, Blair D Grubb3
1Centre for Neuroscience, Xi'an Jiaotong-Liverpool University, Suzhou, China.
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, H2O2 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 H2O2 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.
Insights
Reactive oxygen species (ROS) and TRPA1 channels influence migraine by affecting cortical spreading depression (CSD). Inhibiting ROS and TRPA1 may offer therapeutic benefits for migraine prevention.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Migraine prophylaxis targets the transient receptor potential ankyrin A 1 (TRPA1) channel and calcitonin gene-related peptide (CGRP).
- Understanding the interplay of reactive oxygen species (ROS), TRPA1, and CGRP in cortical spreading depression (CSD) is crucial for migraine research.
Purpose of the Study:
- Investigate the role of TRPA1 in CSD in vivo.
- Explore the mechanisms of ROS/TRPA1/CGRP signaling in regulating cortical susceptibility to CSD.
Main Methods:
- TRPA1 expression was detected using immunohistochemistry.
- CSD was induced and monitored in rats and mouse brain slices using electrophysiology and intrinsic optical imaging.
- ROS levels were assessed via malondialdehyde (MDA) analysis.
Main Results:
- TRPA1 deactivation reduced CSD susceptibility and ipsilateral MDA levels in rats.
- In mouse slices, H2O2 facilitated CSD, an effect blocked by antioxidants and a TRPA1 antagonist.
- CGRP blockade prolonged CSD latency, reversed by H2O2 and a TRPA1 agonist.
Conclusions:
- ROS/TRPA1/CGRP signaling is critical in modulating cortical susceptibility to CSD.
- Inhibiting ROS and deactivating TRPA1 channels show therapeutic potential for stress-triggered migraine via CGRP pathways.
Related Concept Videos
Spreading of Chromatin Modifications
Writers
The writer...
Long-term Depression
Long-term Depression
Calcium Ion Concentration Mechanism
If over...
Freezing Point Depression and Boiling Point Elevation
The boiling point of a liquid is the temperature at which its vapor pressure is equal to ambient atmospheric pressure. Since the vapor pressure of a solution is lowered due to the presence of nonvolatile solutes, it stands to reason that the solution’s boiling point will subsequently be increased. Vapor pressure increases with temperature, and so a solution will require a higher temperature than will pure solvent to achieve any given vapor pressure, including one...
Depressants
Alcohol is a common depressant that can induce a sense of relaxation and reduced inhibition at low doses. Contrary to its occasional...
Paracrine Signaling

