Increased Plasma Matrix Metalloproteinase-9 Levels
Keiko Imamura,MD,PhD;Takao Takeshima,MD,PhD;Emi Fusayasu,MD,PhD;
Background and Objective.—Cortical spreading depression and neurogenic inflammation have been hypothesized to be
key steps in the development of migraine headache. Recent studies have highlighted matrix metalloproteinase-9 (MMP-9) in
cortical spreading depression, neurogenic inflammation, and cerebral ischemia. To seek their possible association, we investi-
gated plasma MMP-9 levels in migraineurs during headache-free periods.
Methods.—Plasma MMP-9 levels in 84 migraine subjects and 61 controls were determined by enzyme-linked immunosor-
bent assay. In addition, 23 patients with tension type headache were included in the study as comparative subjects.
Results.—The MMP-9 levels in migraineurs (42.5 ? 4.6 ng/mL, mean ? SE) were significantly higher than those in con-
trols (25.4 ? 2.7 ng/mL, P < .005). Those levels in tension type headache subjects (24.6 ? 4.8 ng/mL) did not differ from those
in controls.There was no significant difference between subjects having migraine with aura and those without aura.The MMP-9
levels did not correlate with age, duration of illness, frequency of migraine attack, duration of headache attack, or medication
for headache.Mean plasma MMP-9 levels were the highest in subjects from whom blood samples were taken 2-4 days after their
Conclusions.—The degradation of extracellular matrix showing the increase of MMP-9 in migrainurs may be associated
with an abnormality in their blood vessel permeability. MPP-9 plays some role in migraine pathophysiology. Further studies of
MMPs are necessary to elucidate their role.
Key words: cortical spreading depression, gelatinase, ischemia, neurogenic inflammation, migraine
Abbreviations: BBB blood–brain barrier, CSD cortical spreading depression, ECM extracellular matrix, IL-1b interleukin-1b,
MMP matrix metalloproteinase, MMP-9 matrix metalloproteinase-9, TNF-a tumor necrosis factor-a
Migraine headache, a highly prevalent and dis-
abling disease, is characterized by the peripheral and
central sensitization of pain perceptive systems.
Although the pathophysiology is not fully under-
stood, cortical spreading depression (CSD) and neu-
rogenic inflammation have been hypothesized to be
major steps in the development of migraine head-
ache.1,2Recent studies suggests possible association of
migraine and ischemic brain lesions, especially pos-
terior lobes and cerebellum.3The matrix metallopro-
teinases (MMPs) are a family of enzymes with more
than 20 members identified to date that are all extra-
cellular endopeptidases requiring Zn2+. The major
From the Department of Neurology, Institute of Neurological
Sciences, Faculty of Medicine, Tottori University, Yonago,
Address all correspondence to Dr.TakaoTakeshima,Associate
Professor of Neurology, Department of Neurology, Institute of
Neurological Sciences, Faculty of Medicine,Tottori University,
36-1 Nishicho, Yonago, 683-8504, Japan.
Accepted for publication June 19, 2007.
Conflict of Interest: None.
Published by Blackwell Publishing
© 2007 the Authors
Journal compilation © 2008 American Headache Society