The Roles of MMP-9/TIMP-1 in Cerebral Edema Following Experimental Acute Cerebral Infarction in Rats

Authors: Li DD, Song JN, Huang H, Guo XY, An JY, Zhang M, Li Y, Sun P, Pang HG, Zhao YL, Wang JF.

Matrix metalloproteinases 9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1), regulate homeostasis and turnover of the extra cellular matrix (ECM). They play important roles in acute cerebral infarction (ACI). The contributions of MMP-9 and TIMP-1 to the early stages of ACI are not completely understood. This study investigates the time course of MMP-9 and TIMP-1 and their relations to edema after ACI in rats. Serum concentrations of MMP-9 and TIMP-1 protein were measured using ELISA and mRNA level were measured using real-time PCR.Brain samples were harvested and the brain water content (BWC) was measured. Results revealed that MMP-9 concentration increased fast during the first 12h after ACI, while after 12h the increase was much slower. The MMP-9 protein concentration was elevated earlier than the mRNA level. BWC increased starting at 6h after ACI to reach a peak at 12h and decreased back to normal levels at 72h. Both the MMP-9 protein and its mRNA were positively correlated with BWC, however no correlation was found between TIMP-1 levels and BWC. The MMP-9/TIMP-1 protein ratio was more closely correlated with BWC than the MMP-9 concetration. These results indicate that brain edema induced by ACI is associated with increased MMP-9 levels and MMP-9/TIMP-1 ratio in serum.

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