title: Matrix metalloproteinases during and outside of migraine attacks without aura.
abstract: To test the hypothesis that permeability of the blood-brain barrier (BBB) is altered during migraine attack due to enhanced activation of matrix metalloproteinases (MMPs), we investigated MMP-3, MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 in the external jugular vein during and outside of migraine attacks in 21 patients with migraine without aura. In addition, we measured plasma levels of several other proteins including MMP-7, -8, -10 and TIMP-2. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study plasma concentration of MMPs. There was no difference in MMP-9 and TIMP-1 levels between ictal and interictal periods. We found significantly decreased plasma levels of MMP-3 in the external jugular (P = 0.002) and cubital (P = 0.008) vein during attacks compared with outside of attacks. We found no correlation of ictal or interictal MMP-3, MMP-9 and TIMP-1 to migraine duration and frequency analysed in 21 patients (P > 0.05). There was no difference between ictal and interictal plasma levels of MMP-7, -8, -10 and TIMP-2 (P > 0.05). Our data suggest that plasma MMP-9 cannot be used as a biomarker of BBB disruption in migraine without aura. Decreased MMP-3 levels are an interesting and unexpected finding warranting further investigation.
authors.affiliation: Department of Neurology, Glostrup Hospital, Danish Headache Centre, Copenhagen, Denmark. ashina@dadlnet.dk
authors.forename: M
authors.initials: M
authors.lastname: Ashina
authors.forename: J F
authors.initials: JF
authors.lastname: Tvedskov
authors.forename: K
authors.initials: K
authors.lastname: Lipka
authors.forename: J
authors.initials: J
authors.lastname: Bilello
authors.forename: M
authors.initials: M
authors.lastname: Penkowa
authors.forename: J
authors.initials: J
authors.lastname: Olesen
mesh_terms: D000208:Acute Disease; D000328:Adult; D001812:Blood-Brain Barrier / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D005260:Female; D006801:Humans; D007601:Jugular Veins; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D020326:Migraine without Aura / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9