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Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression
Journal article   Open access   Peer reviewed

Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression

Yan Wang, Anne E Tye, Junli Zhao, Dongqing Ma, Ann C Raddant, Fan Bu, Benjamin L Spector, Nolan K Winslow, Minyan Wang and Andrew F Russo
Cephalalgia, Vol.39(3), pp.333-341
03/2019
DOI: 10.1177/0333102416678388
PMCID: PMC5461204
PMID: 27919019
url
https://doi.org/10.1177/0333102416678388View
Published (Version of record) Open Access

Abstract

Objective The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player in migraine. However, the mechanisms underlying the reported elevation of CGRP in the serum and cerebrospinal fluid of some migraineurs are not known. A candidate mechanism is cortical spreading depression (CSD), which is associated with migraine with aura and traumatic brain injury. The aim of this study was to investigate whether CGRP gene expression may be induced by experimental CSD in the rat cerebral cortex. Methods CSD was induced by topical application of KCl and monitored using electrophysiological methods. Quantitative PCR and ELISA were used to measure CGRP mRNA and peptide levels in discrete ipsilateral and contralateral cortical regions of the rat brain 24 hours following CSD events and compared with sham treatments. Results The data show that multiple, but not single, CSD events significantly increase CGRP mRNA levels at 24 hours post-CSD in the ipsilateral rat cerebral cortex. Increased CGRP was observed in the ipsilateral frontal, motor, somatosensory, and visual cortices, but not the cingulate cortex, or contralateral cortices. CSD also induced CGRP peptide expression in the ipsilateral, but not contralateral, cortex. Conclusions Repeated CSD provides a mechanism for prolonged elevation of CGRP in the cerebral cortex, which may contribute to migraine and post-traumatic headache.

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