Expression of tissue inhibitor of metalloproteinases and matrix metalloproteinases in the ischemic brain of photothrombosis model mice

Middle cerebral artery occlusion (MCAO) is the most widely used animal model of ischemic stroke. This model well recapitulates the pathological features of most human cases; however, MCAO is technically difficult to achieve in mice and has some disadvantages for investigating the molecular mechanisms of pathological progression in stroke. The recently developed photothrombosis model may be more suitable for research on the molecular mechanisms of ischemic stroke in mice. Yet, similarities and differences between the photothrombosis and MCAO models are not well characterized. In the present study, we examined the expression of tissue inhibitor of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) in the brains of photothrombosis model mice. Our results indicated that the gene expression of TIMP-1 was upregulated in endothelial cells in the pathological area surrounding the infarction, similar to the MCAO model. Yet, pathologically induced changes in TIMP-1 were not affected by treatment with aspirin or etodolac. Whereas MMP-2 and MMP-8 mRNA were upregulated after infarction in both models, MMP-9 expression, which is induced in the infarct area in the MCAO model, was unchanged in the photothrombosis model. These findings suggest that the expression patterns of TIMP-1 and MMP-9 are regulated independently in photothrombosis model mice.