Matrix metalloproteinases during and outside of migraine attacks without aura
Corresponding Author
M Ashina
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Messoud Ashina MD, PhD, Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Nordre Ringvej 57, Building 23-24, DK-2600 Glostrup, Copenhagen, Denmark. Tel. + 45-4323-2062, fax + 45-4323-3960, e-mail: [email protected]Search for more papers by this authorJF Tvedskov
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Search for more papers by this authorK Lipka
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Search for more papers by this authorJ Bilello
GlaxoSmithKline R&D, Research Triangle Park and
Precision Human Biolaboratory, Durham, NC, USA
Search for more papers by this authorM Penkowa
Section of Neuroprotection, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJ Olesen
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Search for more papers by this authorCorresponding Author
M Ashina
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Messoud Ashina MD, PhD, Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Nordre Ringvej 57, Building 23-24, DK-2600 Glostrup, Copenhagen, Denmark. Tel. + 45-4323-2062, fax + 45-4323-3960, e-mail: [email protected]Search for more papers by this authorJF Tvedskov
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Search for more papers by this authorK Lipka
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Search for more papers by this authorJ Bilello
GlaxoSmithKline R&D, Research Triangle Park and
Precision Human Biolaboratory, Durham, NC, USA
Search for more papers by this authorM Penkowa
Section of Neuroprotection, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJ Olesen
Danish Headache Centre and Department of Neurology, Glostrup Hospital and
Search for more papers by this authorAbstract
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.
References
- 1 Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 1998; 21: 75–80.
- 2 Yong VW, Agrawal SM, Stirling DP. Targeting MMPs in acute and chronic neurological conditions. Neurotherapeutics 2007; 4: 580–9.
- 3 Ethell IM, Ethell DW. Matrix metalloproteinases in brain development and remodeling: synaptic functions and targets. J Neurosci Res 2007; 85: 2813–23.
- 4 Yong VW. The potential use of MMP inhibitors to treat CNS diseases. Expert Opin Investig Drugs 1999; 8: 255–68.
- 5 Goadsby PJ. Migraine pathophysiology. Headache. 2005; 45 (Suppl. 1): S14–24.
- 6 Lauritzen M, Skyhøj Olsen T, Lassen NA, Paulson OB. Changes in regional cerebral blood flow during the course of classic migraine attacks. Ann Neurol 1983; 13: 633–41.
- 7 Leão AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944; 7: 359–90.
- 8 Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 1981; 9: 344–52.
- 9 Sanchez-del-Rio M, Reuter U, Moskowitz MA. New insights into migraine pathophysiology. Curr Opin Neurol 2006; 19: 294–8.
- 10 Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002; 8: 136–42.
- 11 Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H et al. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 2004; 113: 1447–55.
- 12 Shapiro SD. Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr Opin Cell Biol 1998; 10: 602–8.
- 13 Del Zoppo GJ, Milner R, Mabuchi T, Hung S, Wang X, Berg GI, Koziol JA. Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke 2007; 38: 646–51.
- 14 Yong VW, Power C, Forsyth P, Edwards DR. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2001; 2: 502–11.
- 15 Kanesaka T, Mori M, Hattori T, Oki T, Kuwabara S. Serum matrix metalloproteinase-3 levels correlate with disease activity in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2006; 77: 185–8.
- 16 Leira R, Sobrino T, Rodriguez-Yáñez M, Blanco M, Arias S, Castillo J. Mmp-9 immunoreactivity in acute migraine. Headache 2007; 47: 698–702.
- 17 Imamura K, Takeshima T, Fusayasu E, Nakashima K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache 2008; 48: 135–9.
- 18 Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain, 2nd edn. Cephalalgia 2004; 24(Suppl. 1): 9–160.
- 19 Perlee L, Christiansen J, Dondero R, Grimwade B, Lejnine S, Mullenix M et al. Development and standardization of multiplexed antibody microarrays for use in quantitative proteomics. Proteome Sci 2004; 2: 9.
- 20 Schweitzer B, Wiltshire S, Lambert J, O'Malley S, Kukanskis K, Zhu Z et al. Inaugural article: immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection. Proc Natl Acad Sci USA 2000; 97: 10113–19.
- 21 Dohmen C, Sakowitz OW, Fabricius M, Bosche B, Reithmeier T, Ernestus RI et al. Spreading depolarizations occur in human ischemic stroke with high incidence. Ann Neurol 2008; 63: 720–8.
- 22 Kempski O. Cerebral edema. Semin Nephrol 2001; 21: 303–7.
- 23 Hawkins BT, Davis TP. The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57: 173–85.
- 24 Abbott NJ. Inflammatory mediators and modulation of blood–brain barrier permeability. Cell Mol Neurobiol 2000; 20: 131–47.
- 25 Huber JD, Witt KA, Hom S, Egleton RD, Mark KS, Davis TP. Inflammatory pain alters blood–brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol 2001; 280: H1241–8.
- 26 Huber JD, Hau VS, Borg L, Campos CR, Egleton RD, Davis TP. Blood–brain barrier tight junctions are altered during a 72-h exposure to lambda-carrageenan-induced inflammatory pain. Am J Physiol Heart Circ Physiol 2002; 283: H1531–7.
- 27 Brooks TA, Hawkins BT, Huber JD, Egleton RD, Davis TP. Chronic inflammatory pain leads to increased blood–brain barrier permeability and tight junction protein alterations. Am J Physiol Heart Circ Physiol 2005; 289: H738–43.
- 28 Lauritzen M. Cerebral blood flow in migraine and cortical spreading depression. Acta Neurol Scand Suppl 1987; 113: 1–40.
- 29 Moskowitz MA. Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 1993; 43: S16–20.
- 30 Cutrer FM, Sorensen AG, Weisskoff RM, Ostergaard L, Sanchez del Rio M, Lee EJ et al. Perfusion-weighted imaging defects during spontaneous migrainous aura. Ann Neurol 1998; 43: 25–31.
- 31 Crawford JS, Konkol RJ. Familial hemiplegic migraine with crossed cerebellar diaschisis and unilateral meningeal enhancement. Headache 1997; 37: 590–3.
- 32 Arnold G, Reuter U, Kinze S, Wolf T, Einhäupl KM. Migraine with aura shows gadolinium enhancement which is reversed following prophylactic treatment. Cephalalgia 1998; 18: 644–6.
- 33 Filippi M, Yousry T, Campi A, Kandziora C, Colombo B, Voltz R et al. Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS. Neurology 1996; 46: 379–84.
- 34 Rosenberg GA, Estrada E, Kelley RO, Kornfeld M. Bacterial collagenase disrupts extracellular matrix and opens blood–brain barrier in rat. Neurosci Lett 1993; 160: 117–19.
- 35 Savettieri G, Di Liegro I, Catania C, Licata L, Pitarresi GL, D'Agostino S et al. Neurons and ECM regulate occludin localization in brain endothelial cells. Neuroreport 2000; 11: 1081–4.
- 36 Tilling T, Korte D, Hoheisel D, Galla HJ. Basement membrane proteins influence brain capillary endothelial barrier function in vitro. J Neurochem 1998; 71: 1151–7.
- 37 Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC. Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke 1998; 29: 1020–30.
- 38 Penkowa M, Florit S, Giralt M, Quintana A, Molinero A, Carrasco J, Hidalgo J. Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures. J Neurosci Res 2005; 79: 522–34.
- 39 Penkowa M, Giralt M, Moos T, Thomsen PS, Hernández J, Hidalgo J. Impaired inflammatory response to glial cell death in genetically metallothionein-I- and -II-deficient mice. Exp Neurol 1999; 156: 149–64.
- 40 Penkowa M, Hidalgo J. IL-6 deficiency leads to reduced metallothionein-I+II expression and increased oxidative stress in the brain stem after 6-aminonicotinamide treatment. Exp Neurol 2000; 163: 72–84.
- 41 Penkowa M, Poulsen C, Carrasco J, Hidalgo J. M-CSF deficiency leads to reduced metallothioneins I and II expression and increased tissue damage in the brain stem after 6-aminonicotinamide treatment. Exp Neurol 2002; 176: 308–21.
- 42 Imamura K, Takeshima T, Fusayasu E, Nakashima K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache 2008; 48: 135–9.
- 43 Gurney KJ, Estrada EY, Rosenberg GA. Blood–brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol Dis 2006; 23: 87–96.
- 44 Ogata Y, Enghild JJ, Nagase H. Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 1992; 267: 3581–4.
- 45 Samnegard A, Silveira A, Tornvall P, Hamsten A, Ericsson CG, Eriksson P. Lower serum concentration of matrix metalloproteinase-3 in the acute stage of myocardial infarction. J Intern Med 2006; 259: 530–6.
