CGRP, Migraine, and Brain MRI in CADASIL

Goldstein, Eric; Gopal, Neethu; Badi, Mohammed K.; Hodge, David O.; Havenon, Adam de; Glover, Patrick; Durham, Paul L.; Huang, Josephine F.; Lin, Michelle; Baradaran, Hediyeh; Majersik, Jennifer J.; Meschia, James F.

doi:10.1097/nrl.0000000000000478

Cited by 2 publications

(1 citation statement)

References 39 publications

(94 reference statements)

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“…However, it does not seem that CGRP has migraine inducing effects for CADASIL patients compared to the general population. [ 43 ] Even more, reduced vasodilation as consequence of reduced CGRP levels, was associated with worse outcome in CADASIL. [ 44 ] Interestingly, CGRP was reported to stimulate neurogenesis, angiogenesis, to reduce vascular inflammation and cell death, [ 45 ] and to decline (in plasma) during aging.…”

Section: Discussionmentioning

confidence: 99%

Treatment with Cerebrolysin Prolongs Lifespan in a Mouse Model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Kastberger,

Winter,

Brandstätter

et al. 2023

Advanced Biology

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare familial neurological disorder caused by mutations in the NOTCH3 gene and characterized by migraine attacks, depressive episodes, lacunar strokes, dementia, and premature death. Since there is no therapy for CADASIL the authors investigate whether the multi‐modal neuropeptide drug Cerebrolysin may improve outcome in a murine CADASIL model. Twelve‐month‐old NOTCH3R169C mutant mice (n=176) are treated for nine weeks with Cerebrolysin or Vehicle and histopathological and functional outcomes are evaluated within the subsequent ten months. Cerebrolysin treatment improves spatial memory and overall health, reduces epigenetic aging, and prolongs lifespan, however, CADASIL‐specific white matter vacuolization is not affected. On the molecular level Cerebrolysin treatment increases expression of Calcitonin Gene‐Related Peptide (CGRP) and Silent Information Regulator Two (Sir2)‐like protein 6 (SIRT6), decreases expression of Insulin‐like Growth Factor 1 (IGF‐1), and normalizes the expression of neurovascular laminin. In summary, Cerebrolysin fosters longevity and healthy aging without specifically affecting CADASIL pathology. Hence, Cerebrolysin may serve a therapeutic option for CADASIL and other disorders characterized by accelerated aging.

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Section: Discussionmentioning

confidence: 99%

Treatment with Cerebrolysin Prolongs Lifespan in a Mouse Model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Kastberger,

Winter,

Brandstätter

et al. 2023

Advanced Biology

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Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience

Gárate,

Pascual,

Pascual-Mato

et al. 2024

J Headache Pain

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Background Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker. Methods Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age. Results Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2–54.4) and 4.6 (2.4–6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women. Conclusions We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations. Graphical Abstract

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CGRP, Migraine, and Brain MRI in CADASIL

Cited by 2 publications

References 39 publications

Treatment with Cerebrolysin Prolongs Lifespan in a Mouse Model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Treatment with Cerebrolysin Prolongs Lifespan in a Mouse Model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience

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