Relationship between the clinical outcome and the levels of matrix metalloproteinases and their inhibitors in ischemic stroke

PURPOSE: Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of cerebral ischemia, the expression of MMP-2, 9 and TIMP-1 was significantly increased. However, their role in human stroke in vivo remains unknown. Therefore, we sought to determine the temporal profile of MMP and TIMP-1 expression in patients with acute ischemic stroke and to investigate its relationship to stroke severity, prognose and vasculer risk factors.SUBJECTS and METHODS:In this study consecutive patients with an acute stroke were prospectively studied. Totally 120 patients that evaluated within the first 24 hours of stroke onset were included in the study. Control groups that matched with age and sex were also included (n=50). A detailed history of vascular risk factors was obtained from each patient. The neurological examinations of the patients were made in the first day, second day and seventh day in which they were admitted to the clinic. Simultaneously with the examinations, the small amounts of the blood were taken in order to determine the plasma MMP-2,9 and TIMP-1 activity by means of enzyme-linked immunosorbent assay(ELIZA). National Institutes of Health Stroke Scale (NIHSS) was used to determine the severity of stoke. The demographic features of the patients, and the vascular risk factors in past history were performed comprehensively. Patients with a known inflammatory or malignant disease (n=27), and hemorrhagic transformation (n=3) were excluded. CT scanning was carried out in all patients in the first 24 hours.RESULTS: MMP-2, 9 levels of the patients suffering from ischemic CVD in the first day, second day and seventh day were found statically higher than the health of control subjects ( p=0.000, p=0.000). TIMP-1 levels were different than healthy control subjects just in the first day but no other time. There was difference between MMP-9 at the beginning of the study and the severity of stroke at the end of the study (p=0.011). A significant relationship was found between mean MMP-9 and stroke severity (NIHS>8) (p=0.011). No significant relationship was found between MMP-2, TIMP-1 and NIHSS score at any time point, although a close relation appeared between the mean levels of seventh MMP-9 and final NIHSS score (p<.01). A positive correlation was found between the mean levels of seventh day MMP-9 and DM; seventh day TIMP-1 and CAD(coronary arter disease); seventh day TIMP-1 and AF (p=0.042, p=0.04, p=0.003).DISCUSSION: MMPs and TIMPs are involved in the pathophysiology of acute stroke. High plasma MMP-2, 9 and TIMP-1 concentration in the acute ischemic stroke. Our study is important to reveal the role of MMP enzyme system in the pathogenesis beetwen ischemic strok and vasculer risk factors. MMP-9 levels are associated with neurological deficit and worse prognosis. The relationships between the vasculer risk factors and the levels of matrıx metalloproteınases and theır ınhıbıtors in ıschemıc stroke can exhibit alteration in time.KEY WORDS: Matrix metalloproteinases, stroke, NIHSS, TIMP-1