Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits

1994 ◽  
Vol 266 (3) ◽  
pp. H1095-H1102 ◽  
Author(s):  
D. M. Colonna ◽  
W. Meng ◽  
D. D. Deal ◽  
D. W. Busija
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Topical Administration ◽  
Competitive Inhibitor ◽  
Calcitonin Gene Related Peptide ◽  
Cranial Window ◽  
Related Peptide ◽  
Brain Surface ◽  
Calcitonin Gene ◽  
Pial Arterioles

We examined the role of calcitonin gene-related peptide (CGRP) in cortical spreading depression (CSD)-induced dilation of rabbit pial arterioles. In urethan-anesthetized rabbits instrumented with a closed cranial window, CSD induction with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (mean +/- SE, n = 6) microns (a 54 +/- 9% increase). Topical administration of 12.8 microM CGRP-(8-37), a competitive inhibitor of the CGRP receptor, reduced CSD-induced pial dilation from 54 +/- 9% baseline to 33 +/- 9% (P < 0.05). Removal of the receptor antagonist from the brain surface restored CSD-induced dilation to 59 +/- 11% (P < 0.05, compared with the response with the antagonist present). In other animals, we showed that this dose of the CGRP antagonist attenuated arteriolar dilation to topically applied 10(-7) M CGRP (n = 5), but it did not alter arteriolar dilation to arterial hypercapnia. We also evaluated the dilator potency of substance P (SP) compared with CGRP. Dilation with 10(-7) M SP was only 22 +/- 11%, whereas arterioles dilated to 57 +/- 7% above baseline diameter with 10(-7) M CGRP. We conclude that CGRP contributes to the transient arteriolar dilation that is characteristic of CSD.

Cortical Spreading Depression Does Not Result in the Release of Calcitonin Gene-Related Peptide into the External Jugular Vein of the Cat: Relevance to Human Migraine

Cephalalgia ◽  
1993 ◽  
Vol 13 (3) ◽  
pp. 180-183 ◽  
Author(s):  
Richard D Piper ◽  
Lars Edvinsson ◽  
Rolf Ekman ◽  
Geoffrey A Lambert
Keyword(s):  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Jugular Vein ◽  
Calcitonin Gene Related Peptide ◽  
External Jugular Vein ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Vasoactive Peptide ◽  
Stimulation Of

There is circumstantial evidence that cortical spreading depression (SD) may account for the scotoma and the “spreading cortical oligemia” seen during migraine with aura. It has been shown that calcitonin gene-related peptide (CGRP) is increased in blood taken from the external jugular vein (EJV) in humans during migraine and after stimulation of the trigeminal ganglion. To test the hypothesis that cortical SD may elevate the concentration of this vasoactive peptide in the EJV during migraine, we have measured its concentration in the external jugular vein of cats during cortical SD. This study demonstrates that SD has no effect on the concentration of CGRP either during the passage of a wave of spreading depression across the cortex or, 60 min later, during the period of post-SD cortical oligemia.

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

Cephalalgia ◽  
2016 ◽  
Vol 39 (3) ◽  
pp. 333-341 ◽  
Author(s):  
Yan Wang ◽  
Anne E Tye ◽  
Junli Zhao ◽  
Dongqing Ma ◽  
Ann C Raddant ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Calcitonin Gene Related Peptide ◽  
Rat Cerebral Cortex ◽  
Mrna Levels ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Expression ◽  
Cortical Regions

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.

scholarly journals Cortical spreading depression as a site of origin for migraine: Role of CGRP

Cephalalgia ◽  
2018 ◽  
Vol 39 (3) ◽  
pp. 428-434 ◽  
Author(s):  
Liesl N Close ◽  
Sajedeh Eftekhari ◽  
Minyan Wang ◽  
Andrew C Charles ◽  
Andrew F Russo
Keyword(s):  
Cortical Neurons ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Calcitonin Gene Related Peptide ◽  
Trigeminal System ◽  
Migraine Treatment ◽  
Neural Connections ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
A Site

Premise Migraine is a complex neurologic disorder that leads to significant disability, yet remains poorly understood. Problem One potential triggering mechanism in migraine with aura is cortical spreading depression, which can activate the trigeminal nociceptive system both peripherally and centrally in animal models. A primary neuropeptide of the trigeminal system is calcitonin gene-related peptide, which is a potent vasodilatory peptide and is currently a major therapeutic target for migraine treatment. Despite the importance of both cortical spreading depression and calcitonin gene-related peptide in migraine, the relationship between these two players has been relatively unexplored. However, recent data suggest several potential vascular and neural connections between calcitonin gene-related peptide and cortical spreading depression. Conclusion This review will outline calcitonin gene-related peptide-cortical spreading depression connections and propose a model in which cortical spreading depression and calcitonin gene-related peptide act at the intersection of the vasculature and cortical neurons, and thus contribute to migraine pathophysiology.

Nitric oxide and prostaglandins interact to mediate arteriolar dilation during cortical spreading depression

1995 ◽  
Vol 269 (1) ◽  
pp. H176-H181 ◽  
Author(s):  
W. Meng ◽  
D. M. Colonna ◽  
J. R. Tobin ◽  
D. W. Busija
Keyword(s):  
Nitric Oxide ◽  
Cortical Spreading Depression ◽  
Brain Cortex ◽  
Spreading Depression ◽  
Inhibitory Effect ◽  
Onset Latency ◽  
Cranial Window ◽  
Pial Arterioles ◽  
Oxide Synthase ◽  
Arteriolar Diameter

We examined whether blockade of prostaglandin synthesis by indomethacin could attenuate the effect of nitric oxide synthase (NOS) inhibition on cerebral arteriolar dilation during cortical spreading depression (CSD). CSD was induced by microinjection of 5% (670 mM) KCl onto the cerebral cortex of anesthetized adult rabbits. A closed cranial window and intravital microscopy were used to measure pial arteriolar diameter, and NOS activity was determined by the conversion assay of [14C]arginine to [14C]citrulline. CSD dilated pial arterioles by 47 +/- 3% (baseline = 80-88 microns) (n = 21, P < 0.05), and inhibition of NOS by NG-nitro-L-arginine (L-NNA) (15 mg/kg iv) reduced dilation during CSD by over one-half (n = 8, P < 0.05) without altering the onset latency to CSD. After indomethacin administration (15 mg/kg iv), CSD dilated arterioles from 73 +/- 2 to 152 +/- 6 microns (n = 4, P < 0.05). However, after administration of both indomethacin and L-NNA (n = 5), CSD-induced arteriolar dilation was not different from the situation where indomethacin alone was given. Thus indomethacin completely abolished the inhibitory effect of L-NNA on CSD-induced dilation. Administration of L-NNA inhibited NOS activity in brain cortex almost completely (n = 8, P < 0.05), whereas indomethacin itself had no effect (n = 8). In addition, L-NNA inhibited topical acetylcholine (10(-5) M)-induced arteriolar dilation (n = 3, P < 0.05), and this effect was not altered by indomethacin (n = 4). In summary, L-NNA reduced arteriolar dilation during CSD. However, after administration of indomethacin, L-NNA does not reduce CSD-induced arteriolar dilation.

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