Relationship Among The Level Of Serum MMP-9 And TIMP-1 At Acute Stage Of Cerebral Infarction And The Classification Of TOAST And The Significance In Prognosis

objective:Cerebral infarction, also named ischemic stroke, is a common disease in the department of neurology, while the change of permeability of blood-brain barrier (BBB) plays a critical role in cerebral ischemia and ischemical reperfusion injury. Matrix Metalloproteinase-9 (MMP-9) is one of the family of MMPs. It degrades the main component of basal membrane such as typeⅣcollagen, laminin and mucoprotein, et al. and so to cause the permeability of BBB raise. Tissue Inhibitor of Metalloproteinase (TIMP-1) is the endogenous inhibitor of MMP-9. There is dynamic balance between MMP-9 and TIMP-1. The disturbance of the balance may influence the state and prognosis of cerebrovascular disease.The classification of TOAST lays particular emphasis on the cause of ischemic stroke. According to TOAST, ischemic stroke can be divided into five subtypes: Cardioembolism(CE), Large-artery atherosclerosis (LAA), Small-artery occlusion Lacunar(SA), Stroke of other demonstrated etiology(SOE)and Stroke of other undemonstrated etiology(SUE).The objective of this study was to determine and compare the level of serum MMP-9 and TIMP-1 at acute stage of cerebral infarction and to approach the relationship among the level of serum MMP-9, TIMP-1 and the classification of TOAST and the significance in Prognosis.Methods:60 patients with cerebral infarction were included in our study, while 20 healthy people served as the control group. According to TOAST, the patientswere divided into three subtypes: CE, LAA and SA. The serum specimens were gathered for MMP-9 and TIMP-1 determination with ELISA on admission, at the 5th and 10th day of onset. All patients were scored according to the American National Institutes of Health stroke scale (NIHSS) on admission and recorded Barthal Index(BI) on the 1st and 3rd month of onset.Results:1.The relationship between MMP-9 and TOASTThe serum level of MMP-9 increased after cerebral infarction, and were signifycantly higher than those in the control group ( P < 0. 05). There is no significant difference between CE and LAA group ( P>0. 05). MMP-9 in CE and LAA group were significantly higher than those in SA group ( P < 0. 05) . MMP-9 in SA group decreased to normal while was still high in CE and LAA group at the 5th day of onset. At the 10th day MMP-9 in all groups decreased to normal.2.The relationship between TIMP-1 and TOASTThe serum level of TIMP-1 increased after cerebral infarction, and were signifycantly higher than those in the control group ( P < 0. 05). There is no significant difference between CE and LAA group ( P > 0. 05). TIMP - 1 in CE and LAA group were significantly higher than those in SA group ( P < 0. 05) . TIMP-1 in SA group decreased to normal while was still high in CE and LAA group at the 5th day of onset. At the 10th day TIMP-1 in all groups decreased to normal.3.The relationship between MMP-9 and TIMP-1Correlation analysis showed that there was a positive correlation between MMP-9 and TIMP-1 within 24 hours of onset ( r = 0.615 , P < 0.01) .4.The relationship between MMP-9 and the state of cerebral infarction Correlation analysis showed that there was a positive correlation between MMP-9 within 24 hours of onset and NIHSS ( r = 0. 883 , P< 0.01) . It was thus evident that the level of serum MMP-9 within 24 hours of onset can reflect the severity of the state of cerebral infarction to some degree.5. The relationship between MMP-9 and the prognosis of cerebral infarctionAt the 1st month of onset, among 60 cerebral infarction cases there were 35 cases with better prognosis and 25 cases with worse prognosis. The serumlevel of MMP - 9 in the former (5.784±2.448 ng/ml) was significantly lower than those in the latter (8.721±4.004 ng/ml) ( P <0. 05).At the 3rd month of onset , Logistic regression analysis suggested serum level of MMP - 9 within 24 hours of onset as an independent indicator of prognosis. ( BI was regarded as dependent variable, while gender, age, visit time, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the level of serum MMP-9 within 24 hours of onset were regarded as independent variable. ) The Equations: P = 1/ [ 1 +e- (11.832 - 0.079DBP - 0.458MMP-9) ].Conclusions:1.The Serum level of MMP-9 and TIMP-1 increased after cerebral infarction. Compared with SA group, MMP-9 and TIMP-1 were significantly higher in CE and LAA group; MMP-9 and TIMP-1in SA group decreased to normal while was still high in CE and LAA group at the 5th day of onset. At the 10th day MMP-9 and TIMP-1 in all groups decreased to normal.2.Serum level of MMP-9 and TIMP-1 were positive correlation, and the tendency of their variation was similar;3.Serum level of MMP-9 was related to NIHSS, I.e. the severity of the state of cerebral infarction;4.The level of serum MMP-9 within 24 hours of onset can predict prognosis of cerebral infarction independently.