title: Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Repeated CSD provides a mechanism for prolonged elevation of CGRP in the cerebral cortex, which may contribute to migraine and post-traumatic headache.
authors.affiliation: 1 Centre for Neuroscience and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 3 Department of Biological Sciences, Xi'an Jiaotong-Liverpool University (XJTLU), SIP, Suzhou 215123, China.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Tye
authors.affiliation: 1 Centre for Neuroscience and.
authors.forename: Junli
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 1 Centre for Neuroscience and.|2 Neuroscience Program, Departments of.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Ma
authors.affiliation: 4 Molecular Physiology and Biophysics, and.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Raddant
authors.affiliation: 1 Centre for Neuroscience and.|2 Neuroscience Program, Departments of.
authors.forename: Fan
authors.initials: F
authors.lastname: Bu
authors.affiliation: 4 Molecular Physiology and Biophysics, and.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Spector
authors.affiliation: 4 Molecular Physiology and Biophysics, and.
authors.forename: Nolan K
authors.initials: NK
authors.lastname: Winslow
authors.affiliation: 1 Centre for Neuroscience and.|2 Neuroscience Program, Departments of.
authors.forename: Minyan
authors.initials: M
authors.lastname: Wang
authors.affiliation: 3 Department of Biological Sciences, Xi'an Jiaotong-Liverpool University (XJTLU), SIP, Suzhou 215123, China.|4 Molecular Physiology and Biophysics, and.|5 Neurology, University of Iowa, Iowa City, IA 52242, USA.|6 Veterans Affairs Medical Center, Iowa City, IA 52246, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Russo
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; gene expression; migraine; post-traumatic headache; traumatic brain injury