摘要Background Cortical spreading depression can cause migraine attack, and up-regulate matrix metalloproteinase-9 (MMP-9) expression in animal. This study aimed to determine the impact on the structure and function of the blood-brain barrier by measuring plasma MMP-9 levels in patients at the acute and late stages of migraine attacks in order to elucidate the pathological mechanisms involved.Methods We recruited a case-control cohort of 38 adult migraine patients and 20 age- and gender-matched healthy control subjects. Five milliliter blood samples were collected at the acute and late stages of migraine (days 1-7), and also from the control subjects. Solid phase double antibody sandwich enzyme-linked immunosorbent assay was used to determine plasma MMP-9 levels. Statistical analysis was performed using the SAS version 9.1.Results Initial plasma MMP-9 levels of migraine patients were significantly higher than those of controls ((12.612±0.016)μg/L vs. (6.069±0.023) μg/L, respectively, P <0.05). High MMP-9 expression was observed during days 1-6 of migraine attacks, with highest expression occurring on day 3 ((17.524±0.035) μg/L). During attacks, MMP-9 levels were similar in migraine patients with and without aura (P >0.05); in addition, levels were not correlated with degree of headache pain (P >0.05).Conclusions We hypothesize that migraine could lead to increased plasma MMP-9 levels resulting in blood-brain barrier damage. MMP-9 levels increase during days 1-6 of migraine attacks, peaking on day 3. Therefore, MMP-9 could be used as a biological marker to guide treatment of migraine attacks.