TY - JOUR
T1 - Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression
AU - Wang, Yan
AU - Tye, Anne E.
AU - Zhao, Junli
AU - Ma, Dongqing
AU - Raddant, Ann C.
AU - Bu, Fan
AU - Spector, Benjamin L.
AU - Winslow, Nolan K.
AU - Wang, Minyan
AU - Russo, Andrew F.
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Wangwenli Charitable Foundation (RD0006), NIH (NS075599), Veterans Affairs Medical Center (1IO1RX002101), and Department of Defense USAMRAA (W81XWH-16-1-0071).
Publisher Copyright:
© International Headache Society 2016.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - CGRP
KW - gene expression
KW - migraine
KW - post-traumatic headache
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85062418038&partnerID=8YFLogxK
U2 - 10.1177/0333102416678388
DO - 10.1177/0333102416678388
M3 - Article
C2 - 27919019
AN - SCOPUS:85062418038
SN - 0333-1024
VL - 39
SP - 333
EP - 341
JO - Cephalalgia
JF - Cephalalgia
IS - 3
ER -