scholarly journals Efficacy of alpha-calcitonin gene-related peptide in dilating cerebral arteries: protocol for a systematic review and meta-analysis of in vivo animal studies

2016 ◽  
Vol 3 (1) ◽  
pp. e00013 ◽  
Author(s):  
L.M.C. Flynn ◽  
M.R. Macleod ◽  
C.J. Begg ◽  
P.J. Andrews
2000 ◽  
Vol 278 (2) ◽  
pp. H586-H594 ◽  
Author(s):  
Kazunori Toyoda ◽  
Frank M. Faraci ◽  
Andrew F. Russo ◽  
Beverly L. Davidson ◽  
Donald D. Heistad

Overexpression of calcitonin gene-related peptide (CGRP), an extremely potent vasodilator, to blood vessels is a possible strategy for prevention of vasospasm. We constructed an adenoviral vector that encodes prepro-CGRP (Adprepro-CGRP) and examined the effects of gene transfer on cultured cells and cerebral arteries. Transfection of Adprepro-CGRP to Cos-7 and NIH-3T3 cells increased CGRP-like immunoreactivity in media and produced an increase in cAMP in recipient cells. Five days after injection of Adprepro-CGRP into the cisterna magna of rabbits, the concentration of CGRP-like immunoreactivity increased by 93-fold in cerebrospinal fluid. In basilar artery, cAMP increased by 2.3-fold after Adprepro-CGRP compared with a control adenovirus. After transfection of Adprepro-CGRP, contraction of basilar artery in vitro to histamine and serotonin was attenuated, and relaxation to an inhibitor of cyclic nucleotide phosphodiesterase 3-isobutyl-1-methylxanthine was augmented compared with nontransduced arteries or arteries transfected with a control gene. Altered vascular responses were restored to normal by pretreatment with a CGRP1 receptor antagonist CGRP-(8–37). Thus gene transfer of prepro-CGRP in vivo overexpresses CGRP in cerebrospinal fluid and perivascular tissues and modulates vascular tone. We speculate that this approach may be useful in prevention of vasospasm after subarachnoid hemorrhage.


2019 ◽  
Vol 20 (14) ◽  
pp. 3527 ◽  
Author(s):  
I-Hsin Huang ◽  
Po-Chien Wu ◽  
En-Yuan Lin ◽  
Chien-Yu Chen ◽  
Yi-No Kang

We aimed to evaluate the response rate of migraines by using anti-calcitonin gene-related peptide (anti-CGRP) for patients with migraines. We searched three main medical databases up to 29 March 2019. No restriction on language and publication time were applied. Eligible trials included randomized clinical trials investigating a 50%, 75%, and 100% response rate of migraine patients after anti-CGRP intervention. The collected data were dichotomous, and risk ratios (RRs) with a 95% confidence interval (CI) were used to present the quantitative synthesis results. The systematic review identified 16 eligible randomized clinical trials (RCTs) with 9439 patients. Eight of the 16 trials with 2516 patients reported a 50% response rate, and the pooled results showed a significant benefit from anti-CGRP. However, the effects seem to gradually reduce from the first month (RR 1.99, 95% CI 1.59 to 2.49) to the third month (RR 1.48, 95% CI 1.26 to 1.75) of treatment. The magnitude of effect was influenced by the type of anti-CGRP, according to the test for differences between subgroups (I-square = 53%). The funnel plots and Egger’s tests did not show serious small study effects in the results. In conclusion, the current evidences confirmed that anti-CGRP treatment can reduce migraine pain in the short term (within three months), but the long-term effect should be investigated in the future. Moreover, its effects may be influenced by the type and dose of anti-CGRP. Therefore, future studies should make direct comparisons among anti-CGRP medications.


Cephalalgia ◽  
2014 ◽  
Vol 34 (9) ◽  
pp. 695-707 ◽  
Author(s):  
Jakob M Hansen ◽  
Messoud Ashina

Background Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathophysiology. Most studies have focused on CGRP in relation to migraine without aura (MO). About one-third of migraine patients have attacks with aura (MA), and this is a systematic review of the current literature on CGRP and MA. Methods We performed a systematic literature search on MEDLINE for reports of CGRP and MA, covering basic science, animal and human studies as well as randomized clinical trials. Results The literature search identified 594 citations, of which 38 contained relevant, original data. Plasma levels of CGRP in MA patients are comparable to MO, but CGRP levels varied among studies. A number of animal studies, including knock-ins of familial hemiplegic migraine (FHM) genes, have examined the relationship between CGRP and cortical spreading depression. In patients, CGRP does not trigger migraine in FHM, but is a robust trigger of migraine-like headache both in MA and MO patients. The treatment effect of CGRP antagonists are well proven in the treatment of migraine, but no studies have studied the effect specifically in MA patients. Conclusion This systematic review indicates that the role of CGRP in MA is less studied than in MO. Further studies of the importance of CGRP for auras and migraine are needed.


Cephalalgia ◽  
2005 ◽  
Vol 25 (6) ◽  
pp. 424-432 ◽  
Author(s):  
KA Petersen ◽  
E Nilsson ◽  
J Olesen ◽  
L Edvinsson

Calcitonin gene-related peptide (CGRP) and related peptides may be involved in migraine pathogenesis. To understand their vasomotor role in the cerebral circulation, we performed two studies, a pressurized arteriography study of the middle cerebral artery (MCA) and a genuine closed cranial window (gCCW) in vivo study. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-αCGRP, rat-βCGRP, amylin and adrenomedullin were compared with the resting diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries; Emax for αCGRP and βCGRP were 35 ± 0.5% and 10.8 ± 0.2%. These responses were blocked by CGRP8-37. The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes in vessel diameter to intravenously administered αCGRP and βCGRP were compared with pre-infusion baseline. Intravenous infusion of αCGRP and βCGRP in the highest dose induced dilation of the cerebral cortical pial arteries/arterioles of 40.3 ± 7.5% and 49.1 ± 8.4%, respectively. However, this was probably secondary to a decrease in blood pressure of 44.8 ± 3.3 mmHg and 49.2 ± 3.3 mmHg. Our results suggest that CGRP receptors are probably functional on the smooth muscle cells and not on the endothelium of rat cerebral arteries.


Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky

Sign in / Sign up

Export Citation Format

Share Document